Enhancement of oral moxidectin bioavailability in rabbits by lipid co-administration

Abstract

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.

Estimation of absolute oral bioavailability of moxidectin in dogs using a semi‐simultaneous method: influence of lipid co‐administration

“…The absolute bioavailability of oral moxidectin in dogs was very high, regardless of the feeding status (with or without lipids) and our data are at variance with those previously obtained in human and rabbit, which showed that the oral administration of moxidectin together with a fatty meal or a lipid-based formulation substantially increased the systemic concentration of the drug in humans (Cotreau et al, 2003) and rabbits (Bassissi et al, 2004).…”

“…Moxidectin is more lipophilic than ivermectin (McKellar & Benchaoui, 1996) and a co-administration of lipids was shown to increase the oral moxidectin exposure in rabbits (Bassissi et al, 2004) and humans (Cotreau et al, 2003). Thus, the second objective of this study was to assess the influence of lipid co-administration on the pharmacokinetics of orally given moxidectin.…”

Pharmacokinetics of moxidectin following topical administration to New Zealand rabbits

“…Moxidectin is a semi‐synthetic methoxime derivative of nemadectin (Bassissi et al. , 2004, 2006a) and is widely used for the control of gastrointestinal nematodes and ectoparasites in livestock and companion animals (Wagner & Wendlberger, 2000).…”

Assessment of a liposomal formulation of ivermectin in rabbit after a single subcutaneous administration

“…MLs are characterized by a unique long mean residence time (MRT) in the host associated with long-lasting activity when compared with other anthelmintics such as benzimidazoles. The pharmacokinetic behavior of MLs depends upon the route of administration, the formulation used, the animal species, and pathophysiological status of the host (Alvinerie et al 1998;Baggot and McKellar 1994;Bassissi et al 2004b;Hennessy and Alvinerie 2002;Lespine et al 2004;Perez et al 2002). Ivermectin is available for oral, subcutaneous, and topical administration.…”