1. Characterization of the Population Pharmacokinetics of Moxidectin in Adults Infected with Strongyloides Stercoralis: Support for a Fixed-Dose Treatment Regimen.
- Author
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Smit, Cornelis, Hofmann, Daniela, Sayasone, Somphou, Keiser, Jennifer, and Pfister, Marc
- Subjects
MOXIDECTIN ,ADULTS ,PHARMACOKINETICS ,BODY weight ,TREATMENT programs ,HELMINTHIASIS - Abstract
Background: Moxidectin has recently attracted attention as a novel candidate for the treatment of helminth infections, including Strongyloides stercoralis. This study aims to characterize the population pharmacokinetics (PPK) of moxidectin in S. stercoralis-infected adults using a pharmacometric approach, and to perform model-based simulations to explore different drug dosing strategies. Methods: A PPK study embedded in a dose-escalation phase IIa trial was conducted in NamBak, Laos. Eight micro blood samples were collected from each of 96 S. stercoralis-infected adults following a moxidectin dose-ranging study, from 2 to 12 mg. A PPK model was developed using nonlinear mixed-effects modeling, and dosing strategies were explored using simulations in S. stercoralis-infected subjects with varying age and body weight (n = 5000 per dosing strategy). Results: A two-compartment model including delayed absorption with lag-time best described the available PK data. Allometric scaling was applied to account for the influence of body weight. High clearance was found in the infected adults (4.47 L/h [95% confidence interval 3.63–5.39] for a 70 kg individual) compared with that previously reported for healthy adults. Model-based simulations indicated similar variability in mean ± standard deviation area under the curve from time zero to infinity of 1907 ± 1552 and 2175 ± 1670 ng × h/mL in the 60–70 kg weight group, after 8 mg fixed- or weight-based dosing, respectively. Conclusion: We describe the first PPK model for moxidectin in adults with S. stercoralis infection. Equivalent exposures after fixed-dose and weight-dependent dosing strategies support the use of a simple fixed-dose approach, particularly in large-scale treatment programs. Trial Registration: Registered at ClinicalTrials.gov (NCT04056325). [ABSTRACT FROM AUTHOR]
- Published
- 2022
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