title: Drug-drug interaction analysis of pyronaridine/artesunate and ritonavir in healthy volunteers.
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.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Morris
authors.forename: Luis
authors.initials: L
authors.lastname: Lopez-Lazaro
authors.forename: Donald
authors.initials: D
authors.lastname: Jung
authors.forename: Janthima
authors.initials: J
authors.lastname: Methaneethorn
authors.forename: Stephan
authors.initials: S
authors.lastname: Duparc
authors.forename: Isabelle
authors.initials: I
authors.lastname: Borghini-Fuhrer
authors.forename: Rolf
authors.initials: R
authors.lastname: Pokorny
authors.forename: Chang-Sik
authors.initials: CS
authors.lastname: Shin
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fleckenstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D037621:Artemisinins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077332:Artesunate; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D017320:HIV Protease Inhibitors; D009287:Naphthyridines; D000077332:Artesunate; C039060:artenimol; D019438:Ritonavir; C027871:pyronaridine