Publication: Malaria Journal
Abstract
Primaquine is used for radical cure of relapsing malaria but carries toxicity risk in patients with G6PD deficiency, and its two enantiomers are known to differ in pharmacologic and toxicologic properties. This study compared the pharmacokinetics, tissue distribution, and metabolism of individual stable-isotope-labeled primaquine enantiomers in mice following oral dosing, using non-compartmental analysis via the Phoenix WinNonlin platform. The S-enantiomer showed substantially higher plasma and tissue concentrations than the R-enantiomer across most tissues, while a toxic metabolite (carboxyprimaquine) was preferentially generated from the R-enantiomer and another metabolite (primaquine-o-quinone) preferentially from the S-enantiomer. These differential pharmacokinetic and metabolic patterns help explain previously observed differences in antimalarial efficacy and toxicity between primaquine enantiomers, informing consideration of individual enantiomers for clinical use.
Author(s): Fasinu PS, Chaurasiya ND, Dhammika Nanayakkara NP, Wang YH, Bandara Herath HMT, Avula B, McChesney JD, Jollow D, Walker LA, Tekwani BL
Published: February 5, 2022
Phoenix NLME: Enantiomer-Specific Toxicokinetics
Phoenix NLME’s pharmacokinetic analysis distinguished tissue distribution and metabolite formation between two primaquine enantiomers in this study. Phoenix NLME is also available through RsNLME, bringing population PK/PD modeling into R for teams who prefer that environment, within a Phoenix platform cited in more than 33,000 peer-reviewed articles.
