Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors.
Article Details
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von Moltke LL, Greenblatt DJ, Granda BW, Giancarlo GM, Duan SX, Daily JP, Harmatz JS, Shader RI
Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors.
J Clin Pharmacol. 2001 Jan;41(1):85-91. doi: 10.1177/00912700122009728.
- PubMed ID
- 11225565 [ View in PubMed]
- Abstract
The capacity of three clinically available nonnucleoside reverse transcriptase inhibitors (NNRTIs) to inhibit the activity of human cytochromes P450 (CYPs) was studied in vitro using human liver microsomes. Delavirdine, nevirapine, and efavirenz produced negligible inhibition of phenacetin O-deethylation (CYP1A2) or dextromethorphan O-demethylation (CYP2D6). Nevirapine did not inhibit hydroxylation of tolbutamide (CYP2C9) or S-mephenytoin (CYP2C19), but these CYP isoforms were importantly inhibited by delavirdine and efavirenz. This indicates the likelihood of significantly impaired clearance of CYP2C substrate drugs (such as phenytoin, tolbutamide, and warfarin) upon initial exposure to these two NNRTIs. Delavirdine and efavirenz (but not nevirapine) also were strong inhibitors of CYP3A, consistent with clinical hazards of initial cotreatment with either of these drugs and substrates of CYP3A. The in vitro microsomal model provides relevant predictive data on probable drug interactions with NNRTIs when the mechanism is inhibition of CYP-mediated drug biotransformation. However, the model does not incorporate interactions attributable to enzyme induction.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Delavirdine Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Delavirdine Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorDetails Efavirenz Cytochrome P450 2D6 Protein Humans UnknownInhibitorDetails Nevirapine Cytochrome P450 1A2 Protein Humans UnknownInhibitorDetails Nevirapine Cytochrome P450 2D6 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareLacosamideDelavirdine The serum concentration of Lacosamide can be increased when it is combined with Delavirdine.