title: Effects of ritonavir-boosted lopinavir on the pharmacokinetics of quinine.
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. LP V/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 CYP 3A4, UDP-glucuronosyltransferase (UG T), 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.
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. mnyunt@jhsph.edu
authors.forename: M M
authors.initials: MM
authors.lastname: Nyunt
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: El-Gasim
authors.forename: T L
authors.initials: TL
authors.lastname: Parsons
authors.forename: B G
authors.initials: BG
authors.lastname: Petty
authors.forename: C W
authors.initials: CW
authors.lastname: Hendrix
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000962:Antimalarials / Q000493:pharmacokinetics*; D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D006801:Humans; D061466:Lopinavir / Q000493:pharmacokinetics / Q000494:pharmacology*; D008875:Middle Aged; D011803:Quinine / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000962:Antimalarials; D065692:Cytochrome P-450 CYP3A Inhibitors; D061466:Lopinavir; D011803:Quinine; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019438:Ritonavir