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Alshehri, Abdullah, Chhonker, Yashpal S., Bala, Veenu, Edi, Constant, Bjerum, Catherine M., Koudou, Benjamin, John, Lucy N., Mitjà, Oriol, Marks, Michael, King, Christopher L. and Murry, Daryl J. (2023) 'Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis'. PLoS Neglected Tropical Diseases, Vol 17, Issue 6, e0011319.
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Abstract
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
| Item Type: | Article |
|---|---|
| Subjects: | WB Practice of Medicine > Therapeutics > WB 340 Drug Administration WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General) |
| Faculty: Department: | Biological Sciences > Vector Biology Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1371/journal.pntd.0011319 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 02 Jun 2023 08:32 |
| Last Modified: | 02 Jun 2023 08:32 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/22578 |
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