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Population pharmacokinetics of oral ivermectin in venous plasma and dried blood spots in healthy volunteers
Univ Hosp Basel, Div Clin Pharmacol & Toxicol, Basel, Switzerland;Univ Basel, Dept Biomed, Basel, Switzerland.ORCID iD: 0000-0002-7811-3932
Univ Hosp Basel, Div Clin Pharmacol & Toxicol, Basel, Switzerland;Univ Basel, Dept Biomed, Basel, Switzerland.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0003-1258-8297
Univ Basel, Dept Pharmaceut Sci, Biopharm, Basel, Switzerland.
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2019 (English)In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 85, no 3, p. 626-633Article in journal (Refereed) Published
Abstract [en]

Aims

The anthelminthic ivermectin is receiving new attention as it is being repurposed for new indications such as mass drug administrations for the treatment of scabies or in malaria vector control. As its pharmacokinetics are still poorly understood, we aimed to characterize the population pharmacokinetics of ivermectin in plasma and dried blood spots (DBS), a sampling method better suited to field trials, with special focus on the influence of body composition and enterohepatic circulation.

Methods

We performed a clinical trial in 12 healthy volunteers who each received a single oral dose of 12 mg ivermectin, and collected peripheral venous and capillary DBS samples. We determined ivermectin concentrations in plasma and DBS by liquid chromatography tandem mass spectrometry using a fully automated and scalable extraction system for DBS sample processing. Pharmacokinetic data were analysed using non-linear mixed effects modelling.

Results

A two-compartment model with a transit absorption model, first-order elimination, and weight as an influential covariate on central volume of distribution and clearance best described the data. The model estimates (inter-individual variability) for a 70 kg subject were: apparent population clearance 7.7 (25%) l h(-1), and central and peripheral volumes of distribution 89 (10%) l and 234 (20%) l, respectively. Concentrations obtained from DBS samples were strongly linearly correlated (R-2 = 0.97) with plasma concentrations, and on average 30% lower.

Conclusion

The model accurately depicts population pharmacokinetics of plasma and DBS concentrations over time for oral ivermectin. The proposed analytical workflow is scalable and applicable to the requirements of mass drug administrations.

Place, publisher, year, edition, pages
2019. Vol. 85, no 3, p. 626-633
Keywords [en]
Drug analysis, parasitology < Infectious diseases, pharmacokinetics, pharmacometrics, tropical diseases < Infectious diseases
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-379025DOI: 10.1111/bcp.13840ISI: 000458936500016PubMedID: 30566757OAI: oai:DiVA.org:uu-379025DiVA, id: diva2:1295621
Available from: 2019-03-12 Created: 2019-03-12 Last updated: 2019-03-12Bibliographically approved

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Karlsson, Mats OHammann, Felix

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