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

Article Details

Citation

Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ

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

J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739.

PubMed ID
12724045 [ View in PubMed
]
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 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.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
LopinavirCytochrome P450 1A2ProteinHumans
Unknown
Substrate
Inhibitor
Details
LopinavirCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
LopinavirCytochrome P450 2C19ProteinHumans
Unknown
Inhibitor
Details
LopinavirCytochrome P450 2C9ProteinHumans
Unknown
Inhibitor
Inducer
Details
LopinavirCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
LopinavirCytochrome P450 3A Subfamily (Protein Group)Protein groupHumans
No
Inhibitor
Details
LopinavirCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
Drug Interactions
DrugsInteraction
Colchicine
Lopinavir
The serum concentration of Colchicine can be increased when it is combined with Lopinavir.
Itraconazole
Lopinavir
The metabolism of Itraconazole can be decreased when combined with Lopinavir.
Quinidine
Lopinavir
The serum concentration of Quinidine can be increased when it is combined with Lopinavir.
Quinine
Lopinavir
The serum concentration of Quinine can be increased when it is combined with Lopinavir.
Interactions
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