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Pharmacy World and Science

, Volume 24, Issue 3, pp 83–86 | Cite as

Saquinavir soft-gel capsules (Fortovase®) give lower exposure than expected, even after a high-fat breakfast

  • P.W.H. Hugen
  • D.M. Burger
  • P.P. Koopmans
  • J.W.T. Cohen Stuart
  • F.P Kroon
  • R. van Leusen
  • Y.A. Hekster
Article

Abstract

Background: The soft-gel capsule (sgc) of saquinavir has been developed in order to improve the poor oral bioavailability of the original hard-gel capsules. However, in a Dutch study population using saquinavir-sgc plasma levels were lower than expected. We hypothesised that this was caused by differences in the amount of fat in the meals of the study populations. Methods: 8-h steady-state plasma curves after observed ingestion of 1200 mg saquinavir-sgc were recorded, concomitantly with a normal breakfast (600 kcal, 33% fat) on the first day, and a high-fat breakfast (1040 kcal, 54% fat) on the second day. Additionally, a comparison was made between saquinavir hard-gel capsules and saquinavir-sgc with or without grapefruit juice (n=1). Furthermore, a comparison between saquinavir-sgc and ritonavir+saquinavir-sgc 400/400 mg bid was made (n=1). Results: Although saquinavir exposure was improved by fat, grapefruit juice or ritonavir, exposure to saquinavir for all recorded curves was lower than expected. A large proportion of trough concentrations was below the efficacy threshold.Conclusion: Intake of saquinavir-sgc with high-fat meals or grapefruit juice may improve the pharmacokinetic profile. However, plasma concentrations may then still be lower than expected and insufficient for good antiviral efficacy. Probably the only way to reach adequate saquinavir concentrations is by combining saquinavir with ritonavir.

Food Grapefruit juice Pharmacokinetics Saquinavir 

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • P.W.H. Hugen
    • 1
    • 2
  • D.M. Burger
    • 3
    • 2
  • P.P. Koopmans
    • 3
    • 2
  • J.W.T. Cohen Stuart
    • 4
  • F.P Kroon
    • 5
  • R. van Leusen
    • 6
  • Y.A. Hekster
    • 6
  1. 1.Department of Clinical PharmacyUniversity Medical Centre Nijmegen, 533The Netherlands
  2. 2.NijmegenThe Netherlands
  3. 3.Department of General Internal MedicineUniversity Medical Centre Nijmegen, 533The Netherlands
  4. 4.Department of VirologyUniversity Medical Centre UtrechtUtrecht
  5. 5.Leiden University Medical CentreLeiden
  6. 6.Department of Internal MedicineRijnstate HospitalArnhemThe Netherlands

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