Pharmacokinetics of Moxidectin combined with Albendazole or Albendazole plus Diethylcarbamazine for Bancroftian Filariasis.

Abstract

Moxidectin (MOX) is a milbemycin endectocide recently approved by the U.S. FDA for the treatment of onchocerciasis in persons at least 12 years of age. MOX has been shown to have a good safety profile in recent clinical trials. The efficacy of MOX for the treatment of lymphatic filariasis (LF) and its potential use in mass drug administration protocols for the elimination of LF is currently under evaluation. In the context of a clinical trial, we investigated the pharmacokinetics and drug interactions of a combination of MOX plus albendazole (ALB) with or without diethylcarbamazine (DEC) compared to ivermectin (IVM) plus ALB with or without DEC in the following four different treatment arms: (I) IVM (0.2mg/kg) plus DEC (6 mg/kg) and ALB (400mg); (II) IVM plus ALB; (III) MOX (8 mg) plus DEC and ALB; and (IV) MOX plus ALB. Drug concentrations were determined using validated liquid chromatography-mass spectrometric methods. Pharmacokinetic parameters were determined using standard non-compartmental analysis methods. Statistical analysis was performed using JMP software. Fifty-eight of 164 study participants (53 men and five women) were included with ages ranging from 18 to 63 yrs (mean = 37). MOX apparent oral clearance (Cl/F) ranged from 0.7 to 10.8 L/hr with Cmax values ranging from 20.8 to 314.5 ng/mL. The mean (range) area under the curve (AUC)0-∞ for MOX, 3405 ng*hr/mL (742-11376), and IVM 1906 ng*hr/mL (692-5900), varied over a ~15.3 and ~8.5-fold range, respectively. The geometric mean ratio for Cmax, AUC0-t, and AUC0-∞ were within the no-drug interaction range of 80-125% for all drugs. This indicates that the addition of MOX to ALB alone or ALB plus DEC for LF therapy did not alter the drug exposure of co-administered drugs compared to IVM combinations. Clinical Trial Registration: NCT04410406, https://clinicaltrials.gov/.

• Authors: Yashpal S Chhonker, Catherine Bjerum, Veenu Bala, Allassane F Ouattara, Benjamin G Koudou, Toki P Gabo, Abdullah Alshehri, Abdoulaye Meïté, Peter U Fischer, Gary J Weil, Christopher L King, Philip J Budge, Daryl J Murry
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 17 Issue 8 Pg. e0011567 (08 2023) ISSN: 1935-2735 [Electronic] United States
• PMID: 37616301 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Chemical References

• moxidectin
• Albendazole
• Diethylcarbamazine
• Macrolides
• Ivermectin

Topics

• Male
• Female
• Humans
• Elephantiasis, Filarial
• Albendazole
• Diethylcarbamazine
• Macrolides
• Ivermectin