INVESTIGADORES
ALVAREZ Luis Ignacio
artículos
Título:
Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression
Autor/es:
LLOBERAS, M.; ALVAREZ, L.; ENTROCASSO, C.; VIRKEL, G.; BALLENT, M.; MATE, L.; LANUSSE, C.; LIFSCHITZ A.
Revista:
International Journal for Parasitology: Drug and Drug Resistance
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Año: 2012 vol. 3 p. 20 - 27
ISSN:
2211-3207
Resumen:
The high level of resistance to the macrocyclic lactones has encouraged the search for strategies to optimize
their potential as antiparasitic agents. There is a need for pharmaco-parasitological studies addressing
the kinetic-dynamic differences between various macrocyclic lactones under standardized in vivo
conditions. The current work evaluated the relationship among systemic drug exposure, target tissue
availabilities and the pattern of drug accumulation within resistant Haemonchus contortus for moxidectin,
abamectin and ivermectin. Drug concentrations in plasma, target tissues and parasites were measured by
high performance liquid chromatography. Additionally, the efficacy of the three molecules was evaluated
in lambs infected with resistant nematodes by classical parasitological methods. Furthermore, the comparative
determination of the level of expression of P-glycoprotein (P-gp2) in H. contortus recovered from
lambs treated with each drug was performed by real time PCR. A longer persistence of moxidectin
(P < 0.05) concentrations in plasma was observed. The concentrations of the three compounds in the
mucosal tissue and digestive contents were significant higher than those measured in plasma. Drug concentrations
were in a range between 452 ng/g (0.5 day post-treatment) and 32 ng/g (2 days post-treatment)
in the gastrointestinal (GI) contents (abomasal and intestinal). Concentrations of the three
compounds in H. contortus were in a similar range to those observed in the abomasal contents (positive
correlation P = 0.0002). Lower moxidectin concentrations were recovered within adult H. contortus compared
to abamectin and ivermectin at day 2 post-treatment. However, the efficacy against H. contortus
was 20.1% (ivermectin), 39.7% (abamectin) and 89.6% (moxidectin). Only the ivermectin treatment
induced an enhancement on the expression of P-gp2 in the recovered adult H. contortus, reaching higher
values at 12 and 24 h post-administration compared to control (untreated) worms. This comparative
pharmacological evaluation of three of the most used macrocyclic lactones compounds provides new
insights into the action of these drugs.