Effects of ritonavir-boosted lopinavir on the pharmacokinetics of quinine

M. M. Nyunt, Y. Lu, Q. Yu, M. El-Gasim, T. L. Parsons, B. G. Petty, C. W. Hendrix

Research output: Contribution to journalArticlepeer-review

Abstract

The centuries-old antimalarial drug, quinine, continues to play a critical role in the treatment of severe falciparum malaria and uncomplicated malaria in pregnant women. It shares cytochrome P450 (CYP)-mediated metabolic pathways with several commonly used antiretroviral drugs, raising the potential for clinically important drug-drug interactions. A phase I pharmacokinetic study was conducted to assess the impact of long-term use of ritonavir-boosted lopinavir (LPV/r) on quinine pharmacokinetics in healthy volunteers. LPV/r significantly decreased the exposure of quinine and its major active metabolite, 3-hydroxyquinine, in both total and free (unbound) forms. These findings highlight the complex nature of the influence exerted by LPV/r on several of the drug-metabolizing enzymes involved in quinine disposition, including CYP3A4, UDP-glucuronosyltransferase (UGT), and P-glycoprotein (P-gp). A decline in quinine exposure may compromise clinical efficacy. Further studies are warranted to assess changes in quinine pharmacokinetics and treatment outcomes in patients with acute malaria receiving antiretroviral therapy that includes LPV/r.

Original languageEnglish (US)
Pages (from-to)889-895
Number of pages7
JournalClinical pharmacology and therapeutics
Volume91
Issue number5
DOIs
StatePublished - May 2012

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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