Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition

BALLENT, M.; LIFSCHITZ, A.; VIRKEL, G.; MATÉ, L.; LANUSSE, C.

JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS

Wiley Interscience

Año: 2010 p. 252 - 259

0140-7783

The goal of the study was to evaluate the effects of rifampicin (RFP) and phenobarbital (PBT) on the plasma and gastrointestinal disposition kinetics of ivermectin (IVM) subcutaneously administered to Wistar rats. Fifty seven (57) rats were used. Animals in Group I were the non-induced (control) group. Those in Groups II and III received a treatment with RFP (160 mg/day) and PBT (35 mg/day), respectively, both given orally during 8 consecutive days as induction regimen. The IVM pharmacokinetic study was started 24 h after the RFP and PBT last administration. Animals received IVM (200 µg/kg) subcutaneously injected. Rats were sacrificed between 6h and 3d after IVM administration. Blood and samples of liver tissue, intestinal wall and luminal content of jejunum were collected from each animal. IVM concentrations were measured by high performance liquid chromatography. IVM disposition kinetics in plasma and tissues was clearly modified by the PBT treatment but not by RFP. Despite the enhanced CYP3A activity observed after the pre-treatment with RPF and PBT, there were not marked changes on the percentages of IVM metabolites recovered from the bloodstream in induced and non-induced animals. An enhanced P-glycoprotein-mediated intestinal transport activity in pre-treated animals (particularly in PBT pre-treated rats) may account to explain the drastic changes observed on IVM disposition.