Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration



This article is corrected by:

  1. Errata: Errata Volume 69, Issue 5, 571, Article first published online: 12 April 2010

Professor Cyprian O. Onyeji, PhD, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife 2200055, Osun State, Nigeria.
Tel: + 234 803 705 8720



• Malaria is widespread across some areas of the world, most of which also bear the brunt of the human immunodeficiency virus (HIV) pandemic, resulting in a high incidence of co-infection of both diseases.

• Ritonavir, a HIV protease inhibitor, and quinine, an antimalarial agent effective against multidrug-resistant Plasmodium falciparum, are likely to be administered concurrently for treatment of patients with HIV and malaria.

• Both drugs are metabolized to a significant extent by CYP3A4 and ritonavir is a potent inhibitor of this enzyme.


• With increasing access to antiretroviral drugs, it is important that potential interactions between therapies for HIV and malaria infections are investigated.

• In this study, concurrent administration of ritonavir with quinine was found to be associated with marked elevation in the plasma levels of the antimalarial and a pronounced decrease in plasma concentrations of 3-hydroxyquinine, the major metabolite of quinine.

• There was also a modest but significant increase (P < 0.05) in plasma concentrations of ritonavir in the presence of quinine.

AIMS To evaluate the pharmacokinetic interactions between ritonavir and quinine in healthy volunteers.

METHODS Ten healthy volunteers were each given 600-mg single oral doses of quinine alone, ritonavir alone (200 mg every 12 h for 9 days), and quinine in combination with ritonavir, in a three-period pharmacokinetic nonrandomized sequential design study. Quinine was co-administered with the 15th dose of ritonavir. Blood samples collected at predetermined time intervals were analysed for ritonavir, quinine and its major metabolite, 3-hydroxyquinine, using a validated high-performance liquid chromatography method.

RESULTS Concurrent ritonavir administration resulted in about fourfold increases in both the Cmax and AUCT[Cmax 2.79 ± 0.22 vs. 10.72 ± 0.32 mg l−1, 95% confidence interval (CI) 7.81, 8.04; AUC 50.06 ± 2.52 vs. 220.47 ± 6.68 mg h−1 l−1, 95% CI 166.3, 175.3], a significant increase (P < 0.01) in the elimination half-life (11.15 ± 0.80 vs. 13.37 ± 0.33 h, 95% CI 1.64, 2.77) and about a 4.5-fold decrease in CL/F (12.01 ± 0.61 vs. 2.71 ± 0.09 l h−1) of quinine. Also, with ritonavir, there was a pronounced reduction of AUC(metabolite)/AUC(unchanged drug) ratio of quinine (1.35 ± 0.10 vs. 0.13 ± 0.02) along with a marked decrease in Cmax (1.80 ± 0.12 vs. 0.96 ± 0.09 mg l−1) and AUC0–48h (62.80 ± 6.30 vs. 25.61 ± 2.44 mg h−1 l−1) of the metabolite. Similarly, quinine caused modest but significant increases (P < 0.01) in the Cmax, AUC and elimination T½ of ritonavir.

CONCLUSIONS Downward dosage adjustment of quinine appears necessary when concurrently administered with ritonavir.