Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes.

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Lejus C, Fautrel A, Malledant Y, Guillouzo A

Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes.

Biochem Pharmacol. 2002 Oct 1;64(7):1151-6. doi: 10.1016/s0006-2952(02)01226-1.

PubMed ID

12234619 [ View in PubMed

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Abstract

While almost anesthetics are metabolized by the cytochrome P450 (CYP) 3A4, some major volatile ones such as halothane and sevoflurane are metabolized by CYP2E1 in humans. To determine whether 2,6-diisopropylphenol (propofol), a widely used intravenous anesthetic agent, known to inhibit CYP3A4 and CYP1A2, also inhibits CYP2E1, 6-OH hydroxylation of chlorzoxazone, a prototypical CYP2E1 substrate, was estimated using two pools of human microsomes and one pool of porcine microsomes from seven livers. Basal human enzyme activities were characterized by a V(max) of 1426+/-230 and 288+/-29 pmol min(-1)mg(-1) protein and a K(m) of 122+/-47 and 149+/-42 microM, while the corresponding porcine activities were associated with a V(max) of 352+/-42 pmol min(-1)mg(-1) protein and a K(m) of 167+/-38 microM. A competitive inhibition of CYP2E1 by propofol was observed with low inhibition constants in the therapeutic range in both porcine (19 microM) and human (48 microM) liver microsomes. These in vitro results suggest that propofol could have a protective effect on toxic metabolite activation of compounds catalyzed by CYP2E1.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Propofol	Cytochrome P450 2E1	Protein	Humans	Unknown	Inhibitor	Details