The Antiparasitic Moxidectin: Safety, Tolerability, and Pharmacokinetics in Humans

Abstract

A study in healthy male volunteers was completed to evaluate the safety, tolerability, and pharmacokinetics of a single oral dose of the antiparasitic moxidectin (MOX). This drug is registered worldwide as a veterinary antiparasitic agent for use in companion and farm animals. This is the first study of MOX in humans. All subjects were between the ages of 18 and 45 years, with normal cardiac, hematologic, hepatic, and renal function. Doses of MOX studied were 3, 9, 18, and 36 mg in cohorts of 6 subjects each (5:1, MOX:placebo). At the 9-mg and 36-mg doses, two separate cohorts were completed, one in the fasted state and one after the consumption of a high-fat breakfast. For all other cohorts, administration was in the fasted state. Safety and tolerability were assessed by physical examinations, ongoing evaluation of adverse events (AEs), and measurement of laboratory values. Pharmacokinetic (PK) samples were collected just prior to dosing and at various time points until 80 days postdose. Safety assessments from all dose groups studied suggested that MOX was generally safe and well tolerated, with a slightly higher incidence of transient, mild, and moderate central nervous system AEs as the dose increased as compared to placebo. The PKs of MOX were dose proportional within the dose range studied, and the elimination half-life (t1/2 elim) was long (mean: 20.2-35.1 days). At the 9-mg and 36-mg doses, a high-fat breakfast was shown to delay and increase the overall absorption but did not increase maximal concentrations when compared to administration in the fasted state. In summary, the results from this study indicate that MOX is safe and well tolerated in humans between the doses of 3 mg and 36 mg.

Repositioning of an existing drug for the neglected tropical disease Onchocerciasis

“…In fact, both ivermectin (Fig. 1A) (7) and its analogue, moxidectin (30), were originally marketed as veterinary anthelmintics (20). Ivermectin targets the O. volvulus microfilariae and has an embryostatic effect on the adult female worms (8,31).…”

Helminth infections: the great neglected tropical diseases

“…New classes of cysteine protease inhibitors are being developed as anthelminthic and antiprotozoal drugs (163), and other studies have indicated the efficacy of triclabendazole for infection with the difficult to treat liver fluke Fasciola hepatica (164,165). Human and animal studies also suggest that tribendimidine will prove effective against food-borne flukes (166) and the drug moxidectin might become an alternative to ivermectin for the treatment of filarial infections (167). Finally, based on the observation that the filarial parasites Wuchereria bancrofti and Onchocerca volvulus harbor bacterial endosymbionts of the genus Wolbachia and depend on these endosymbionts for normal metabolic and reproductive activities, there is excitement about the development and use of antibiotics to target adult filarial worms (168).…”

In Vitro Efficacy of Moxidectin versus Ivermectin against Sarcoptes scabiei

“…For human scabies, ivermectin is the only licensed oral acaricide, with moxidectin under recent consideration for development as an alternative to ivermectin (1). As moxidectin has a prolonged plasma half-life (t 1/2 ) in humans (29 to 47 days versus 14 h) (2)(3)(4), it is anticipated that it may be more suitable than ivermectin as a single oral dose, providing coverage over the entire mite life cycle.…”