Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes

Li Qun Yang, Wei Feng Yu, Yun Fei Cao, Bin Gong, Qing Chang, Guang Shun Yang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Aim: Hepatic cytochrome P450 isoenzymes constitute a superfamily of hemoproteins that play a major role in the metabolism of endogenous compounds and in the detoxification of xenobiotic molecules. P450 3A4 is one of the most important forms in human being, and mediates the metabolism of around 70 % of therapeutic drugs and endogenous compounds. Propofol, a widely used intravenous anesthetic drug, is known to inhibit cytochrome P450 activities in isolated rat hepatocytes. The goal of this study was to evaluate the potential efficacy of propofol on P450 3A4 in a dose-dependent manner to understand its drug-drug interaction. Methods: Hepatocytes were isolated from liver specimens from hepatic angioma patients undergone hepatic surgery. Primary incubated hepatocytes were treated with 0, 0.01, 0.05, 0.1, 0.5, and 1.0 mM propofol for 24 hours. P450 3A4 activity was measured with Nash's colorimetry. The protein expression was assessed by Western blot analysis. Results: A dose-dependent inhibitory effect of propofol was observed in cytochrome P450 3A4 activity. A minimal dosage of propofol (0.01 mM) induced a significant inhibition of P450 3A4 activity, although its regular dosages (0.01-0.1 mM) showed no inhibitory effect on the cellular protein expression of P450 3A4. Conclusion: Propofol may be a potential CYP3A4 inhibitor as this anesthetic can inhibit isoenzyme activity significantly and reduce the metabolic rate of CYP3A4 substrates. This inhibition occurs at post-expression level, and concentration of propofol used clinically does not affect CYP3A4 protein expression, propofol may thus induce drug interaction of cytochrome P450 3A4 activity at the dosage used clinically.

Original languageEnglish (US)
Pages (from-to)1959-1962
Number of pages4
JournalWorld Journal of Gastroenterology
Volume9
Issue number9
StatePublished - Sep 15 2003
Externally publishedYes

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Cytochrome P-450 CYP3A
Propofol
Hepatocytes
Liver
Drug Interactions
Cytochrome P-450 Enzyme System
Isoenzymes
Anesthetics
Intravenous Anesthetics
Colorimetry
Proteins
Xenobiotics
Hemangioma
Pharmaceutical Preparations
Western Blotting

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Yang, L. Q., Yu, W. F., Cao, Y. F., Gong, B., Chang, Q., & Yang, G. S. (2003). Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes. World Journal of Gastroenterology, 9(9), 1959-1962.

Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes. / Yang, Li Qun; Yu, Wei Feng; Cao, Yun Fei; Gong, Bin; Chang, Qing; Yang, Guang Shun.

In: World Journal of Gastroenterology, Vol. 9, No. 9, 15.09.2003, p. 1959-1962.

Research output: Contribution to journalArticle

Yang, LQ, Yu, WF, Cao, YF, Gong, B, Chang, Q & Yang, GS 2003, 'Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes', World Journal of Gastroenterology, vol. 9, no. 9, pp. 1959-1962.
Yang, Li Qun ; Yu, Wei Feng ; Cao, Yun Fei ; Gong, Bin ; Chang, Qing ; Yang, Guang Shun. / Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes. In: World Journal of Gastroenterology. 2003 ; Vol. 9, No. 9. pp. 1959-1962.
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abstract = "Aim: Hepatic cytochrome P450 isoenzymes constitute a superfamily of hemoproteins that play a major role in the metabolism of endogenous compounds and in the detoxification of xenobiotic molecules. P450 3A4 is one of the most important forms in human being, and mediates the metabolism of around 70 {\%} of therapeutic drugs and endogenous compounds. Propofol, a widely used intravenous anesthetic drug, is known to inhibit cytochrome P450 activities in isolated rat hepatocytes. The goal of this study was to evaluate the potential efficacy of propofol on P450 3A4 in a dose-dependent manner to understand its drug-drug interaction. Methods: Hepatocytes were isolated from liver specimens from hepatic angioma patients undergone hepatic surgery. Primary incubated hepatocytes were treated with 0, 0.01, 0.05, 0.1, 0.5, and 1.0 mM propofol for 24 hours. P450 3A4 activity was measured with Nash's colorimetry. The protein expression was assessed by Western blot analysis. Results: A dose-dependent inhibitory effect of propofol was observed in cytochrome P450 3A4 activity. A minimal dosage of propofol (0.01 mM) induced a significant inhibition of P450 3A4 activity, although its regular dosages (0.01-0.1 mM) showed no inhibitory effect on the cellular protein expression of P450 3A4. Conclusion: Propofol may be a potential CYP3A4 inhibitor as this anesthetic can inhibit isoenzyme activity significantly and reduce the metabolic rate of CYP3A4 substrates. This inhibition occurs at post-expression level, and concentration of propofol used clinically does not affect CYP3A4 protein expression, propofol may thus induce drug interaction of cytochrome P450 3A4 activity at the dosage used clinically.",
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