INVESTIGADORES
IMPERIALE Fernanda Andrea
artículos
Título:
Loperamide-induced enhancement of moxidectin availability in cattle
Autor/es:
LIFSCHITZ, A.; VIRKEL, G.; SALLOVITZ, J.; IMPERIALE, F.; PIS, A.; LANUSSE, C.
Revista:
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
Editorial:
Blackwell Synergy
Referencias:
Año: 2002 p. 111 - 120
ISSN:
0140-7783
Resumen:
Moxidectin (MXD) is a milbemycin endectocide compound active at extremely
low dosages against a wide variety of nematode and arthropod parasites.
Different pharmacological approaches are currently being tested to delay the
bile-faecal elimination and to obtain increased systemic availability for endectocide
molecules in ruminants. Loperamide (LPM) is an opioid derivative, whose
main pharmacological action is to abolish intestinal propulsive peristaltic waves.
The influence of LPM on the pattern of faecal excretion of MXD and on its plasma
disposition following intravenous (i.v.) and subcutaneous (s.c.) administrations
to cattle was evaluated in the current work. Parasite-free calves were treated
with MXD given either alone at 200 lg/kg by i.v. (Experiment 1) and s.c.
(Experiment 2) administrations or coadministered with LPM subcutaneously
injected at 0.4 mg/kg. Blood and faecal samples were collected over a period of
20 (Experiment 1) and 40 (Experiment 2) days post-treatment. The recovered
plasma and faecal samples were extracted and analysed by high-performance
liquid chromatography (HPLC) using fluorescence detection. Significantly
higher MXD plasma concentrations were obtained after the coadministration of
MXD + LPM compared with treatments with MXD alone by both routes. The
higher MXD plasma concentration profiles measured after the coadministration
with LPM accounted for the significantly higher AUC values obtained following
the i.v. (> 46%) and s.c. (> 38%) treatments. A reduced MXD body clearance
was observed in the presence of LPM. The appearance of MXD in faeces was
significantly delayed after the i.v. and s.c. coadministrations of MXD with LPM
(T1/2app ¼ 5.87 and 10.6 h, respectively) than that observed after the treatment
with MXD alone (T1/2app ¼ 3.48 and 5.12 h). A delayed MXD peak concentration
in faeces collected from MXD + LPM-treated animals compared with
those receiving MXD alone, was observed. The delayed intestinal transit time
caused by LPM and a potential competition between MXD and LPM for the
P-glycoprotein-mediated bile/intestinal secretion processes, may account for the
enhanced MXD systemic availability measured in cattle in the current work.lg/kg by i.v. (Experiment 1) and s.c.
(Experiment 2) administrations or coadministered with LPM subcutaneously
injected at 0.4 mg/kg. Blood and faecal samples were collected over a period of
20 (Experiment 1) and 40 (Experiment 2) days post-treatment. The recovered
plasma and faecal samples were extracted and analysed by high-performance
liquid chromatography (HPLC) using fluorescence detection. Significantly
higher MXD plasma concentrations were obtained after the coadministration of
MXD + LPM compared with treatments with MXD alone by both routes. The
higher MXD plasma concentration profiles measured after the coadministration
with LPM accounted for the significantly higher AUC values obtained following
the i.v. (> 46%) and s.c. (> 38%) treatments. A reduced MXD body clearance
was observed in the presence of LPM. The appearance of MXD in faeces was
significantly delayed after the i.v. and s.c. coadministrations of MXD with LPM
(T1/2app ¼ 5.87 and 10.6 h, respectively) than that observed after the treatment
with MXD alone (T1/2app ¼ 3.48 and 5.12 h). A delayed MXD peak concentration
in faeces collected from MXD + LPM-treated animals compared with
those receiving MXD alone, was observed. The delayed intestinal transit time
caused by LPM and a potential competition between MXD and LPM for the
P-glycoprotein-mediated bile/intestinal secretion processes, may account for the
enhanced MXD systemic availability measured in cattle in the current work.AUC values obtained following
the i.v. (> 46%) and s.c. (> 38%) treatments. A reduced MXD body clearance
was observed in the presence of LPM. The appearance of MXD in faeces was
significantly delayed after the i.v. and s.c. coadministrations of MXD with LPM
(T1/2app ¼ 5.87 and 10.6 h, respectively) than that observed after the treatment
with MXD alone (T1/2app ¼ 3.48 and 5.12 h). A delayed MXD peak concentration
in faeces collected from MXD + LPM-treated animals compared with
those receiving MXD alone, was observed. The delayed intestinal transit time
caused by LPM and a potential competition between MXD and LPM for the
P-glycoprotein-mediated bile/intestinal secretion processes, may account for the
enhanced MXD systemic availability measured in cattle in the current work.T1/2app ¼ 5.87 and 10.6 h, respectively) than that observed after the treatment
with MXD alone (T1/2app ¼ 3.48 and 5.12 h). A delayed MXD peak concentration
in faeces collected from MXD + LPM-treated animals compared with
those receiving MXD alone, was observed. The delayed intestinal transit time
caused by LPM and a potential competition between MXD and LPM for the
P-glycoprotein-mediated bile/intestinal secretion processes, may account for the
enhanced MXD systemic availability measured in cattle in the current work.T1/2app ¼ 3.48 and 5.12 h). A delayed MXD peak concentration
in faeces collected from MXD + LPM-treated animals compared with
those receiving MXD alone, was observed. The delayed intestinal transit time
caused by LPM and a potential competition between MXD and LPM for the
P-glycoprotein-mediated bile/intestinal secretion processes, may account for the
enhanced MXD systemic availability measured in cattle in the current work.