The repurposing of ivermectin for malaria:a prospective pharmacokinetics-based virtual clinical trials assessment of dosing regimen options

Abstract

Ivermectin has demonstrated many successes in the treatment of a range of nematode infections. Considering the increase in malaria resistance attention has turned towards ivermectin as a candidate for repurposing for malaria. This study developed and validated an ivermectin physiologically-based pharmacokinetic model in healthy adults (20-50 years) and paediatric (3-5 years/15-25 kg) subjects and in a representative adult malaria population group (Thailand). Dosing optimisation demonstrated a twice daily for 3- or 5-day regimens would provide a time above the LC50 of more than 7 days for adult and paediatric. Furthermore, to address the occurrence of CYP450-induction often encountered with antiretroviral agents, simulated drug-drug interaction studies with efavirenz highlighted that a 1 mg/kg once daily dose for five days would counteract the increased ivermectin hepatic clearance and enable a time above LC50 of 138.8 hours in adults and 141.2 hours in paediatric subjects. It was also demonstrated that dosage regimen design would require consideration of the age-weight geographical relationship of the subjects, with a dosage regimen for a representative Thailand population group requiring at least a single daily dose for 5 days to maintain ivermectin plasma concentrations and a time above LC50 similar to that in healthy adults.

Publication DOI: https://doi.org/10.1016/j.xphs.2018.03.026
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Aston University (General)
Additional Information: © 2018, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: Physiologically-based pharmacokinetics,pharmacokinetics,drug resistance,Onychomycosis,n-silico modelling
Publication ISSN: 1520-6017
Last Modified: 30 Oct 2024 08:34
Date Deposited: 06 Apr 2018 07:45
Full Text Link:
Related URLs: https://www.sci ... 022354918301990 (Publisher URL)
PURE Output Type: Article
Published Date: 2018-08-01
Published Online Date: 2018-04-05
Accepted Date: 2018-03-30
Authors: Badhan, Raj (ORCID Profile 0000-0002-0904-9324)
Zakaria, Zaril
Olafuyi, Olusola

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