Chloramphenicol Is a Potent Inhibitor of Cytochrome P450 Isoforms CYP2C19 and CYP3A4 in Human Liver Microsomes

Ji-Young Park, Kyoung Ah Kim, Su Lyun Kim

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The inhibitory effect of chloramphenicol on human cytochrome P450 (CYP) isoforms was evaluated with human liver microsomes and cDNA-expressed CYPs. Chloramphenicol had a potent inhibitory effect on CYP2C19-catalyzed S-mephytoin 4′-hydroxylation and CYP3A4-catalyzed midazolam 1-hydroxylation, with apparent 50% inhibitory concentrations (inhibitory constant [Ki] values are shown in parentheses) of 32.0 (7.7) and 48.1 (10.6) μM, respectively. Chloramphenicol also weakly inhibited CYP2D6, with an apparent 50% inhibitory concentration (Ki) of 375.9 (75.8) μM. The mechanism of the drug interaction reported between chloramphenicol and phenytoin, which results in the elevation of plasma phenytoin concentrations, is clinically assumed to result from the inhibition of CYP2C9 by chloramphenicol. However, using human liver microsomes and cDNA-expressed CYPs, we showed this interaction arises from the inhibition of CYP2C19- not CYP2C9-catalyzed phenytoin metabolism. In conclusion, inhibition of CYP2C19 and CYP3A4 is the probable mechanism by which chloramphenicol decreases the clearance of coadministered drugs, which manifests as a drug interaction with chloramphenicol.

Original languageEnglish
Pages (from-to)3464-3469
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume47
Issue number11
DOIs
Publication statusPublished - 2003 Nov 1
Externally publishedYes

Fingerprint

Cytochrome P-450 CYP3A
Liver Microsomes
Chloramphenicol
Cytochrome P-450 Enzyme System
Protein Isoforms
Phenytoin
Hydroxylation
Drug Interactions
Inhibitory Concentration 50
Complementary DNA
Cytochrome P-450 CYP2D6
Midazolam
Cytochrome P-450 CYP2C19
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Chloramphenicol Is a Potent Inhibitor of Cytochrome P450 Isoforms CYP2C19 and CYP3A4 in Human Liver Microsomes. / Park, Ji-Young; Kim, Kyoung Ah; Kim, Su Lyun.

In: Antimicrobial Agents and Chemotherapy, Vol. 47, No. 11, 01.11.2003, p. 3464-3469.

Research output: Contribution to journalArticle

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