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

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

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 × 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.

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Authors and Affiliations

  1. Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

    Natascia Corti, Antje Heck, Alexander Jetter, Bruno Stieger & Christiane Pauli-Magnus

  2. Institute for Clinical Chemistry, University Hospital Zurich, 8091, Zurich, Switzerland

    Katharina Rentsch

  3. University Children’s Hospital, Zurich, Switzerland

    Walter Zingg

  4. Clinical Trial Unit, University Hospital Basel, Basel, Switzerland

    Christiane Pauli-Magnus

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  1. Natascia Corti
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  2. Antje Heck
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  3. Katharina Rentsch
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  4. Walter Zingg
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  5. Alexander Jetter
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  6. Bruno Stieger
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  7. Christiane Pauli-Magnus
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Correspondence to Natascia Corti.

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Corti, N., Heck, A., Rentsch, K. et al. Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers. Eur J Clin Pharmacol 65, 999–1006 (2009). https://doi.org/10.1007/s00228-009-0683-y

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  • DOI: https://doi.org/10.1007/s00228-009-0683-y

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