title: Effect of multiple doses of rifampin on the [14C N-methyl] erythromycin breath test in healthy male volunteers.
abstract: The erythromycin breath test (EBT), which measures 14CO2 produced from [14C N-methyl] erythromycin, is one of the most frequently employed measures to examine drug interactions involving cytochrome P450 3A4 (CYP3A). However, the reproducibility and reliability of this test, and the effects of drugs that alter CYP3A activity, continue to be defined. In this study, the reproducibility of the EBT was evaluated in eight healthy volunteers before and after oral administration of 600 mg of rifampin daily for 8 days. Two sequential EBT determinations performed 5 days apart before rifampin administration were highly reproducible. Rifampin induced CYP3A, reflected in a mean percent (+/- standard deviation) increase in EBT values of 86 +/- 30%. Recovery of enzyme function after discontinuation of rifampin for 17 days was manifested as a return of EBT values to preinduction levels. These results support the utility of EBT as a valid, reproducible, and reliable measure of CYP3A activity in vivo.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman.
authors.forename: M N
authors.initials: MN
authors.lastname: Gharaibeh
authors.forename: L P
authors.initials: LP
authors.lastname: Gillen
authors.forename: B
authors.initials: B
authors.lastname: Osborne
authors.forename: J I
authors.initials: JI
authors.lastname: Schwartz
authors.forename: S A
authors.initials: SA
authors.lastname: Waldman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000378:metabolism / Q000494:pharmacology*; D001944:Breath Tests / Q000379:methods*; D002250:Carbon Radioisotopes; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D004917:Erythromycin / Q000378:metabolism; D005069:Evaluation Studies as Topic; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D015203:Reproducibility of Results; D012293:Rifampin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000904:Antibiotics, Antitubercular; D002250:Carbon Radioisotopes; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D012293:Rifampin