1921
Volume 93, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

This study aimed to investigate the pharmacokinetic interactions between quinine and lopinavir boosted with ritonavir (LPV/r) in healthy Thai adults (8 males and 12 females). Period 1 (day 1): subjects received a single oral dose of 600 mg quinine sulfate. Period 2: subjects received LPV/r (400/100 mg) twice daily. Period 3: subjects received a single quinine sulfate dose plus LPV/r twice a day. Intensive blood sampling was performed during each phase. Quinine AUC (area under the plasma concentration–time curve from time 0 to 48 hours), AUC (area under the plasma concentration–time curve from time 0 to infinity), and (maximum concentration over the time-span specified), were 56%, 57%, and 47% lower, respectively, in the presence of LPV/r. 3-Hydroxyquinine AUC, AUC, and were significantly lower and the metabolite-to-parent ratio was significantly reduced. Lopinavir and ritonavir exposures were not significantly reduced with quinine coadministration, but of both drugs were significantly lower. The geometric mean ratio (GMR) and 90% CI of AUC, AUC, and for quinine, 3-hydroxyquinine, lopinavir, and ritonavir lay outside the bioequivalent range of 0.8–1.25. Drug treatments during all periods were generally well tolerated. The reduction in systemic exposure of quinine and 3-hydroxyquinine with concomitant LPV/r use raises concerns of suboptimal exposure. Studies in HIV/malaria coinfection patients are needed to determine the clinical impact to decide if any change to the quinine dose is warranted.

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  • Received : 19 Jun 2015
  • Accepted : 16 Aug 2015
  • Published online : 09 Dec 2015

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