Drug-drug interaction analysis of pyronaridine/artesunate and ritonavir in healthy volunteers

30 Mar 2012

Carrie A. Morris, Luis Lopez-Lazaro, Donald Jung, Janthima Methaneethorn, Stephan Duparc, Isabelle Borghini-Fuhrer, Rolf Pokorny, Chang-Sik Shin and Lawrence Fleckenstein

The American Journal of Tropical Medicine and Hygiene

DOI: 10.4269/ajtmh.2012.11-0558

Abstract

A multiple dose, parallel group study was conducted to assess for a drug-drug interaction between the pyronaridine/artesunate (PA) combination antimalarial and ritonavir. Thirty-four healthy adults were randomized (1:1) to receive PA for 3 days or PA with ritonavir (100 mg twice daily for 17 days, PA administered on Days 8-10). Pharmacokinetic parameters for pyronaridine, artesunate, and its active metabolite dihydroartemisinin (DHA) were obtained after the last PA dose and for ritonavir on Days 1 and 10. Ritonavir coadministration did not markedly change pyronaridine pharmacokinetics but resulted in a 27% increase in artesunate area under the curve (AUC) and a 38% decrease in DHA AUC. Ritonavir exposure was increased 3.2-fold in the presence of PA. The only relevant safety observations were increases in liver enzymes, only reaching a clinically significant grade in the PA + ritonavir arm. It was concluded that coadministered ritonavir and PA interact to alter exposure to artesunate, DHA, and ritonavir itself.

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