Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis.

Autor: Alshehri A; Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.; Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia., Chhonker YS; Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America., Bala V; Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America., Edi C; Centre Suisse de Recherche Scientifique en Côte d'Ivoire, Abidjan, Côte d'Ivoire., Bjerum CM; Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America., Koudou BG; Centre Suisse de Recherche Scientifique en Côte d'Ivoire, Abidjan, Côte d'Ivoire.; Université Nangui Abrogoua, Abidjan, Côte d'Ivoire.; Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom., John LN; Barcelona Institute for Global Health-University of Barcelona, Barcelona, Spain.; School of Medicine and Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea.; National Department of Health, Port Moresby, Papua New Guinea., Mitjà O; Barcelona Institute for Global Health-University of Barcelona, Barcelona, Spain.; School of Medicine and Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea., Marks M; London School of Hygiene and Tropical Medicine, London, United Kingdom.; Hospital for Tropical Diseases, London, United Kingdom.; Division of Infection and Immunity, University College London, London, United Kingdom., King CL; Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.; Veterans Affairs Research Service, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, United States of America., Murry DJ; Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2023 Jun 01; Vol. 17 (6), pp. e0011319. Date of Electronic Publication: 2023 Jun 01 (Print Publication: 2023).
DOI: 10.1371/journal.pntd.0011319
Abstrakt: Background: Ivermectin (IVM) is a broad-spectrum anthelmintic drug used to treat diseases caused by filarial worms, such as onchocerciasis and lymphatic filariasis (LF). IVM is part of a triple-drug therapy used by the Mass Drug Administration (MDA) as a preventive strategy to eradicate LF in sub-Saharan Africa. The drug shows high variability in drug exposure in previous pharmacokinetic studies. This study aims to build a population pharmacokinetic (PopPK) model to identify and quantify the possible sources of the variability of IVM exposure after a single-oral dose in LF-infected subjects and healthy individuals.
Methodology / Principal Findings: In this analysis, 724 samples were collected from treatment-naïve Wuchereria bancrofti-infected (n = 32) and uninfected (n = 24) adults living in Côte d'Ivoire who had received one dose of IVM as a part of triple-drug therapy. PopPK analysis was conducted using Phoenix NLME 8.3 software. The Monte Carlo simulation based on the final model was performed to simulate drug exposure among different dosing groups (200 μg/kg, 18 mg, and 36 mg). A two-compartment model with zero-order dose input into the absorption compartment with a lag time function followed by first-order absorption and linear elimination best described the IVM's pharmacokinetic (PK) parameters. The final model identifies that the PK parameters of IVM are not affected by LF infection. Sex was a significant covariate on the peripheral volume of distribution (Vp/F, 53% lower in men than in women). IVM drug exposure shows linear pharmacokinetic behavior among the simulated dosing groups with similar drug exposure based on sex.
Conclusion/significance: We have developed a PopPk model to describe and identify possible sources of the variability of IVM exposure. To our knowledge, this is the first PopPK study of IVM in patients with LF.
Trial Registration: NCT02845713; NCT03664063.
Competing Interests: The authors declare that there are no conflicts of interest.
(Copyright: © 2023 Alshehri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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