Relative Bioavailability of Liquid and Tablet Formulations of the Antiparasitic Moxidectin

Abstract

The antiparasitic agent moxidectin is under development for the treatment of onchocerciasis. As the first-in-human study of moxidectin used a liquid formulation but other trials used tablets, a study was performed to determine the relative bioavailability of the 2 formulations and to gain more information about the pharmacokinetics of moxidectin. Fifty-eight healthy male participants were randomized to receive open-label moxidectin (10 mg) as a tablet (n = 29) or liquid (n = 29) formulation. The mean ± SD pharmacokinetic parameters observed following administration of the tablet were peak concentration (Cmax) 67.1 ± 27.4 ng/mL, time to peak concentration (tmax) 3.2 ± 1.4 hours, area under the concentration time curve (AUC) 4403 ± 2360 ng·h/mL, apparent volume of distribution 3635 ± 1720 L, oral clearance 2.83 ± 1.25 L/h, and elimination half-life 1032 ± 502 hours. The Cmax and AUC observed following administration of the liquid formulation were 28.6% and 28.8% higher, respectively, and tmax 0.9 hours shorter compared with tablets. No serious adverse events (AEs) were observed. The most commonly reported AEs were headache, infection, diarrhea, asthenia, myalgia, and dizziness during the inpatient phase and flu syndrome, headache, and infection during the 6-month outpatient phase. There was no difference in reporting of these AEs between formulations.

Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder

“…Importantly, MOX is currently undergoing clinical development as an alternative to ivermectin for treating the parasite Onchocerca volvulus , and to date, no significant clinical abnormalities or serious adverse events have been reported over for these investigations (Cotreau et al, 2003; Korth-Bradley et al, 2012). The faster onset time, robust efficacy and favorable safety profile continue to support the development of MOX as a novel pharmacotherapy for the treatment of AUD.…”

“…Notably, MOX is now being developed as an alternative therapy to ivermectin as an anti-parasitic agent for humans. To date, no significant clinical abnormalities have been reported (Cotreau at al., 2003; Korth-Bradley et al, 2012). With MOX becoming approved for human use, it could represent another avermectin candidate that could be repurposed as a pharmacotherapy for AUD.…”

A Review of Scabies: An Infestation More than Skin Deep

“…Moxidectin is a newer agent that offers promise; it has better retention in the skin and a much longer half-life (more than 20 days, compared with 14 h for ivermectin) meaning that a single dose may be enough to eliminate infestation [79, 80]. It also appears to prevent reinfestation for a longer period of time after treatment, compared with ivermectin.…”

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.…”