INVESTIGADORES
ALVAREZ Luis Ignacio
artículos
Título:
Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep
Autor/es:
LIFSCHITZ, A.; ENTROCASSO, C.; ALVAREZ, L.; LLOBERAS, M.; BALLENT, M.; MANAZZA, J.; VIRKEL, G.; BORDA, B.; LANUSSE, C.
Revista:
VETERINARY PARASITOLOGY
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Año: 2010
ISSN:
0304-4017
Resumen:
The in vivo co-administration of ivermectin (IVM) with P-glycoprotein
(P-gp) modulator agents has been shown to enhance the systemic availability of
the antiparasitic drug. However, there is not sufficient evidence on the impact
that this type of drug-drug interaction may have on the in vivo efficacy against resistant nematodes in ruminant species.
The current work reports on the effects of loperamide (LPM), a P-gp modulating
agent, on both IVM kinetic behaviour and anthelmintic activity in infected
lambs. Eighteen (18) lambs naturally infected with IVM resistant
gastrointestinal nematodes were allocated into three (3) experimental groups.
Group A remained as untreated control. Animals in Groups B and C received IVM
(200 µg/kg, subcutaneously) either alone or co-administered with LPM (0.2
mg/kg, twice every 12 h), respectively. Individual faecal samples were
collected from experimental animals at days -1 and 14 post-treatment to perform
the faecal eggs count reduction test (FECRT). Blood
samples were collected between 0 and 14 days post-treatment and IVM
plasma concentrations were determined by HPLC. Additionally, at day 14
post-treatment, animals from all experimental groups were sacrificed and adult
gastrointestinal nematode counts were performed. FECRT values increased from 79 (IVM alone) to 96 % (IVM+LPM). Haemonchus contortus showed to be highly
resistant to IVM. The IVM alone treatment was completely ineffective (0 %
efficacy) against adult H. contortus.
This efficacy value increased up to
72.2% in the presence of LPM. The efficacy against Trichostrongylus
colubriformis increased from 77.9 % (IVM alone) to 96.3 % (IVM+LPM). The
described favorable tendency towards improved anthelmintic efficacy was in
agreement with the enhanced IVM plasma
availability (P<0.05) and prolonged elimination half-life (P<0.05)
induced by LPM in infected lambs. A
LPM-induced P-gp modulation increases IVM systemic exposure in the host but
also it may reduce P-gp efflux transport over-expressed in target resistant
nematodes.