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Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir

Weemhoff, James L, von Moltke, Lisa L, Richert, Clemens, Hesse, Leah M, Harmatz, Jerold S, Greenblatt, David J·2003·Journal of Pharmacy and Pharmacology
DOI 10.1211/002235702739
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Abstract

The influence of the viral protease inhibitor lopinavir on the activity of six human cytochrome P450 (CYP) enzymes was evaluated in a model system using human liver microsomes. Column chromatography methodology was developed to separate lopinavir from ritonavir starting from the commercially available lopinavir-ritonavir combination dosage form. Lopinavir produced negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2C19 and 2D6. However, lopinavir was an inhibitor of CYP3A. At 250 μM triazolam (the CYP3A index substrate), the mean (± s.e., n = 4) IC50 versus triazolam α-hydroxylation (where IC50 is the concentration producing a 50% decrement in reaction velocity) was 7.3 (± 0.5) μM. Pre-incubation of lopinavir with microsomes prior to addition of triazolam yielded a significantly lower IC50 of 4.1 (± 0.5) μM. This is consistent with mechanism-based inhibition of human CYP3A by lopinavir. Although lopinavir is less potent than ritonavir as an inhibitor of CYP3A, lopinavir is nonetheless likely to contribute to net CYP3A inhibition in-vivo during treatment with the lopinavir-ritonavir combination.

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Research works printed but not linked: 33

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Metadata

Authors
Weemhoff, J. L., von Moltke, L. L., Richert, C., Hesse, L. M., Harmatz, J. S., & Greenblatt, D. J.
Affiliations
  • Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, and the Division of Clinical Pharmacology, Tufts-New England Medical Center , Boston, MA,
  • Department of Chemistry, University of Konstanz ,
Venue
Journal of Pharmacy and Pharmacology
Publisher
Oxford University Press (OUP)
Published
2003-03-01
Volume
55
Issue
3
Pages
381-386
ISSN
  • 0022-3573
  • 2042-7158
DOI
10.1211/002235702739
Cited by
25
References
0
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)

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CoChat. (2026). Citation check: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. https://app.cochat.ai/papers/10.1211/002235702739
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Weemhoff, J. L., von Moltke, L. L., Richert, C., Hesse, L. M., Harmatz, J. S., & Greenblatt, D. J. (2003). Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. Journal of Pharmacy and Pharmacology. https://doi.org/10.1211/002235702739

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