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- Duthaler, Urs, et al.
(författare)
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Population pharmacokinetics of oral ivermectin in venous plasma and dried blood spots in healthy volunteers
- 2019
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 85:3, s. 626-633
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe 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.ResultsA 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.
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| 2. |
- Duthaler, Urs, et al.
(författare)
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The effect of food on the pharmacokinetics of oral ivermectin
- 2020
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 75:2, s. 438-440
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ivermectin is an older anthelminthic agent that is being studied more intensely given its potential for mass drug administration against scabies, malaria and other neglected tropical diseases. Its pharmacokinetics (PK) remain poorly characterized. Furthermore, the majority of PK trials are performed under fasted-state dosing conditions, and the effect of food is therefore not well known. To better plan and design field trials with ivermectin, a model that can account for both conditions would be valuable.Objectives: To develop a PK model and characterize the food effect with single oral doses of ivermectin.Patients and methods: We performed a population-based PK analysis of data pooled from two previous trials of a single dose of 12mg ivermectin, one with dosing after a high-fat breakfast (n=12) and one with fasted-state dosing (n=3).Results: The final model described concentration-time profiles after fed and fasted dosing accurately, and estimated the food effect associated with relative bioavailability to 1.18 (95% CI 1.10-1.67).Conclusions: In this analysis, the effect of a high-fat breakfast compared with a fasted-state administration of a single oral dose of 12mg ivermectin was minimal.
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