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

Corti, Natascia ; Heck, Antje ; Rentsch, Katharina ; Zingg, Walter ; Jetter, Alexander ; Stieger, Bruno ; Pauli-Magnus, Christiane

In: European Journal of Clinical Pharmacology, 2009, vol. 65, no. 10, p. 999-1006

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    Title
    • Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers
    Author
    • Corti, Natascia. Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
    • Heck, Antje. Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
    • Rentsch, Katharina. Institute for Clinical Chemistry, University Hospital Zurich, 8091, Zurich, Switzerland
    • Zingg, Walter. University Children's Hospital, Zurich, Switzerland
    • Jetter, Alexander. Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
    • Stieger, Bruno. Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
    • Pauli-Magnus, Christiane. Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • European Journal of Clinical Pharmacology, 2009, vol. 65, no. 10, p. 999-1006. Springer-Verlag
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:316012
    Summary
    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 1,000mg mebendazole or 400mg albendazole (2 × 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 (8days) treatment with ritonavir 200mg 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