Publication: Pharmacokinetic interactions between primaquine and pyronaridine-artesunate in healthy adult Thai subjects
Issued Date
2015-01-01
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ISSN
10986596
00664804
00664804
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2-s2.0-84920179913
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.59, No.1 (2015), 505-513
Suggested Citation
Podjanee Jittamala, Sasithon Pukrittayakamee, Elizabeth A. Ashley, François Nosten, Borimas Hanboonkunupakarn, Sue J. Lee, Praiya Thana, Kalayanee Chairat, Daniel Blessborn, Salwaluk Panapipat, Nicholas J. White, Nicholas P.J. Day, Joel Tarningb Pharmacokinetic interactions between primaquine and pyronaridine-artesunate in healthy adult Thai subjects. Antimicrobial Agents and Chemotherapy. Vol.59, No.1 (2015), 505-513. doi:10.1128/AAC.03829-14 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/36863
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Title
Pharmacokinetic interactions between primaquine and pyronaridine-artesunate in healthy adult Thai subjects
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Abstract
© 2015 Jittamala et al. Pyronaridine-artesunate is a newly introduced artemisinin-based combination treatment which may be deployed together with primaquine. A single-dose, randomized, three-sequence crossover study was conducted in healthy Thai volunteers to characterize potential pharmacokinetic interactions between these drugs. Seventeen healthy adults received a single oral dose of primaquine alone (30 mg base) and were then randomized to receive pyronaridine-artesunate alone (540-180 mg) or pyronaridineartesunate plus primaquine in combination, with intervening washout periods between all treatments. The pharmacokinetic properties of primaquine, its metabolite carboxyprimaquine, artesunate, its metabolite dihydroartemisinin, and pyronaridine were assessed in 15 subjects using a noncompartmental approach followed by a bioequivalence evaluation. All drugs were well tolerated. The single oral dose of primaquine did not result in any clinically relevant pharmacokinetic alterations to pyronaridine, artesunate, or dihydroartemisinin exposures. There were significantly higher primaquine maximum plasma drug concentrations (geometric mean ratio, 30%; 90% confidence interval [CI], 17% to 46%) and total exposures (15%; 6.4% to 24%) during coadministration with pyronaridine-artesunate than when primaquine was given alone. Pyronaridine, like chloroquine and piperaquine, increases plasma primaquine concentrations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01552330.)