Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers

• Published in: European journal of clinical pharmacology Vol. 65; no. 10; pp. 999 - 1006
• Main Authors: Corti, Natascia, Heck, Antje, Rentsch, Katharina, Zingg, Walter, Jetter, Alexander, Stieger, Bruno, Pauli-Magnus, Christiane
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.10.2009; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Adult; Albendazole - administration & dosage; Albendazole - adverse effects; Albendazole - pharmacokinetics; Anti-HIV Agents - pharmacology; Antiparasitic Agents - administration & dosage; Antiparasitic Agents - adverse effects; Antiparasitic Agents - pharmacokinetics; Antiretroviral drugs; Bioavailability; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Drug Interactions; Drug therapy; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - pharmacology; Humans; Male; Mebendazole - administration & dosage; Mebendazole - adverse effects; Mebendazole - pharmacokinetics; Medical sciences; Middle Aged; Parasitic diseases; Pharmacokinetics and Disposition; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Reference Values; Ritonavir - administration & dosage; Ritonavir - pharmacology; Time Factors; Mebendazole; Benzimidazoles; Drug interaction; Albendazole; Ritonavir; Human; Antiretroviral agent; Anthelmintic; Healthy subject; Enzyme; Enzyme inhibitor; Peptidases; Benzimidazole derivatives; Hydrolases; Parasiticide; Antiviral; Pharmacokinetics; Protease inhibitor
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-009-0683-y

Background Benzimidazoles are often used concomitantly with protease inhibitors in patients with helminthic disease and HIV infection. Low bioavailability and extensive first-pass metabolism make benzimidazoles prone to pharmacokinetic drug interactions. The aim of the present study was to investigate potential drug interactions between the benzimidazoles albendazole and mebendazole and the potent CYP3A4 inhibitor ritonavir. Methods Sixteen healthy volunteers were administered a single oral dose of 1,000 mg mebendazole or 400 mg albendazole (2 x n = 8). AUC, Cmax, and t₁/₂ of mebendazole, albendazole, and albendazole sulfoxide were studied in absence and after short-term (2 doses) and long-term (8 days) treatment with ritonavir 200 mg bid. Results Pharmacokinetic parameters of albendazole and mebendazole were not changed by short-term administration of ritonavir. However, long-term administration of ritonavir resulted in significant changes in albendazole and mebendazole disposition, with a significant decrease in AUC₀₋₂₄ (27 and 43% of baseline for albendazole and mebendazole, respectively) and Cmax (26 and 41% of baseline, respectively). Conclusion The AUC₀₋₂₄ of benzimidazoles decreased after long-term use of ritonavir, while no changes in pharmacokinetic profiles were observed under short-term administration. These findings might help to optimize benzimidazole efficacy when used in combination with protease inhibitors.