Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors.

Article Details

Citation

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
DrugEnzymeKindOrganismPharmacological ActionActions
DelavirdineCytochrome P450 2C9ProteinHumans
Unknown
Inhibitor
Details
DelavirdineCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
EfavirenzCytochrome P450 2D6ProteinHumans
Unknown
Inhibitor
Details
NevirapineCytochrome P450 1A2ProteinHumans
Unknown
Inhibitor
Details
NevirapineCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Inhibitor
Details
Drug Interactions
DrugsInteraction
Lacosamide
Delavirdine
The serum concentration of Lacosamide can be increased when it is combined with Delavirdine.
Interactions
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