No abstract

Dyslipidemia led to major changes in moxidectin plasma distribution and in drug disposition. Therefore, a high variability in moxidectin disposition might be expected in humans or animals liable to develop dyslipidemia, with a possible impact on the efficacy and safety of this class of drugs.

Moxidectin is a member of the macrocyclic lactone family of drugs widely used for the control of internal and external parasites. Because moxidectin is highly lipophilic, we suspect that lymphatic transport influences the intestinal absorption of oral formulations of the drug. We studied the influence of lipid coadministration on the pharmacokinetics of an oral formulation of moxidectin in rabbits. Ten rabbits were orally administered 0.3 mg kg À1 moxidectin with or without sunflower oil. Moxidectin and triglyceride were analyzed in plasma over 23 days. Sunflower oil coadministration significantly increased the area under the plasma concentration-time curve of moxidectin (98%, P<0.05) and prolonged its mean residence time from 1.52 days to 2.12 days (P<0.04). Simultaneously, an increase in plasma triglyceride was observed in response to oil administration. It is suggested that lipid administration increases the systemic availability of oral moxidectin by enhancing the extent of intestinal lymphatic transport of the drug. Lipid-based formulations should improve the bioavailability of moxidectin in rabbits.