ritonavir and pyronaridine

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.

Topics: Adolescent; Adult; Antimalarials; Area Under Curve; Artemisinins; Artesunate; Drug Interactions; Female; HIV Protease Inhibitors; Humans; Male; Middle Aged; Naphthyridines; Ritonavir; Young Adult

Topics: Africa; Amides; Amodiaquine; Artesunate; Atazanavir Sulfate; Carbamates; Clinical Trials as Topic; COVID-19; COVID-19 Drug Treatment; COVID-19 Vaccines; Cytidine; Drug Approval; Drug Evaluation, Preclinical; Drug Repositioning; Drug Therapy, Combination; Humans; Hydroxylamines; Imidazoles; Ivermectin; Naphthyridines; Nitro Compounds; Pregnenediones; Pyrazines; Pyrrolidines; Ritonavir; Sample Size; Thiazoles; Valine; World Health Organization