Effects of metronidazole on hepatic CYP3A4 activity.
OBJECTIVE
To evaluate the effect of a short course of oral metronidazole, commonly used for bowel-preparation regimens, on hepatic cytochrome P450 (CYP) 3A4 activity, as measured by the [14C N-methyl]-erythromycin breath test (ERMBT) in healthy volunteers.


METHODS
Prospective, nonrandomized, interventional study


METHODS
University-affiliated, community, teaching hospital.


METHODS
Five healthy male volunteers.


METHODS
Subjects underwent a baseline ERMBT in the morning before receiving three oral doses of metronidazole 500 mg administered at 3 P.M., 7 P.M., and 11 P.M. Repeat ERMBTs were performed at 24, 72, and 96 hours after the initial ERMBT. Changes in ERMBT values were compared with baseline results using Freidman's repeated-measures analysis of variance on ranks.


RESULTS
The ERMBT values did not change significantly compared with baseline (p=0.82). Median (range) ERMBT values expressed as a percentage of baseline at 24, 72, and 96 hours were 110.3 (96.2-136.9), 101.3 (99.3-115.0), and 101.8 (95.5-116.3), respectively


CONCLUSIONS
A short course of oral metronidazole does not result in a significant change in hepatic CYP3A4 activity as measured by the ERMBT.
Haas
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Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, 14260-1200, USA. haas@acsu.buffalo.edu
Kaufman
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DiCenzo
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D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001944:Breath Tests; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D004917:Erythromycin / Q000493:pharmacokinetics; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008745:Methylation; D008795:Metronidazole / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D008795:Metronidazole; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human