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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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

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 microM triazolam (the CYP3A index substrate), the mean (+/- s.e., n = 4) IC50 versus triazolam alpha-hydroxylation (where IC50 is the concentration producing a 50% decrement in reaction velocity) was 7.3 (+/- 0.5) microM. Pre-incubation of lopinavir with microsomes prior to addition of triazolam yielded a significantly lower IC50 of 4.1 (+/- 0.5) microM. 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.[1]


  1. Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. Weemhoff, J.L., von Moltke, L.L., Richert, C., Hesse, L.M., Harmatz, J.S., Greenblatt, D.J. J. Pharm. Pharmacol. (2003) [Pubmed]
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