INVESTIGADORES
IMPERIALE Fernanda Andrea
artículos
Título:
Loperamide modifies the tissue disposition kinetics of ivermectin in rats
Autor/es:
LIFSCHITZ, A.; VIRKEL, G.; SALLOVITZ, J.; PIS, A.; IMPERIALE, F.; LANUSSE, C.
Revista:
JOURNAL OF PHARMACY AND PHARMACOLOGY
Referencias:
Año: 2004 vol. 56 p. 61 - 67
ISSN:
0022-3573
Resumen:
Ivermectin (IVM) is a broad-spectrum antiparasitic drug extensively used in human and veterinary
medicine that is largely excreted in bile and faeces. Loperamide (LPM) is an opioid derivative that
reduces gastrointestinal secretions and motility. Both IVM and LPM have been reported to act as
P-glycoprotein substrates (P-GP). The goal of the present work was to study the LPM-induced modifications
to the pattern of tissue distribution for IVM. Thirty-six Wistar male rats were randomly allocated
to two groups (n¼18) and treated subcutaneously with IVM alone or co-administered with LPM. Rats
were killed at different times post-treatment and samples (blood and tissues) were collected and
analyzed by HPLC. The presence of LPM induced a marked enhancement in the IVM plasma concentrations,
resulting in a significantly higher area under concentration time curve (AUC) value (P < 0.01) than
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
were killed at different times post-treatment and samples (blood and tissues) were collected and
analyzed by HPLC. The presence of LPM induced a marked enhancement in the IVM plasma concentrations,
resulting in a significantly higher area under concentration time curve (AUC) value (P < 0.01) than
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver
tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal
lumen content. The ratio between IVM concentrations in the large intestinal luminal content and
plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal
transit time caused by LPMaccounting for an extended plasma-intestine recycling time, and a potential
competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may
account for the enhanced IVM systemic availability reported in the current study.
statistically significant differences in drug availability in the large intestinal wall after both treatments.
However, LPM induced a marked decrease