Differential sex-related pattern on intestinal P-glycoprotein activity: impact on ivermectin secretion along the digestive tract.

A. LIFSCHITZ, M. BALLENT, G. VIRKEL, J. SALLOVITZ, C. CERIANI, H. SOLANA AND C. LANUSSE.

Turin – Italy

Congreso; 10th International Congress. European Association for Veterinary Pharmacology and Toxicology (EAVPT); 2006

. European Association for Veterinary Pharmacology and Toxicology (EAVPT

The role of P-glycoprotein (P-gp) on the pharmacokinetic disposition of different drugs has been demonstrated. Differences on P-gp function among animal species have also been shown (1). The antiparasitic drug ivermectin (IVM) is a P-gp substrate and the involvement of P-gp on the IVM intestinal excretion has been recently demonstrated (2, 3). Sex-related differences on the disposition of IVM in cattle (4) and selamectin in dogs (5) have been observed. A suitable approach to assess the in vivo P-gp function/activity is the evaluation of the effects of known P-gp inhibitors on drug disposition. The ratio between IVM concentrations in the intestinal wall and luminal content may be used as an estimator of the capacity of inhibition of P-gp modulator agents on the in vivo gastrointestinal (GI) secretion. The aim of the current study was to evaluate in vivo the influence of animal gender and P-gp modulation on the in vivo GI secretion of IVM using a laboratory animal model. Complementary work included the comparative assessment of P-gp expression in liver tissue and along different sections of the GI tract in female and male sheep.