title: Influence of rifampin on the pharmacokinetics of pefloxacin.
abstract: Pefloxacin and rifampin are frequently associated in the antibiotic therapy of deep-seated, and especially bone-located, infections. The influence of rifampin, a potent drug metabolism enzyme inducer, on the pharmacokinetics of pefloxacin was studied in a randomized crossover trial involving eight young healthy male volunteers. Every volunteer received either pefloxacin alone (period A) or pefloxacin after a 10-day induction by rifampin (period B) given as a 900 mg daily oral dose, and both periods were separated by a 3-week washout period. During both periods, pefloxacin was given during 3 days as a 400 mg b.i.d. oral dose (six doses) followed by a 400 mg intravenous dose on the fourth day. The kinetics of pefloxacin are significantly influenced by rifampin: The minimum (12-hour) plasma concentration, area under the concentration-time curve, and elimination half-life decreased respectively from 4.26 +/- 1.57 to 2.70 +/- 1.00 mg/L, 78.91 +/- 22.82 to 57.81 +/- 16.69 mg.hr/L, 14.46 +/- 3.46 to 10.08 +/- 2.44 hours (p less than 0.05). The renal clearance of pefloxacin was unchanged, but the plasma clearance increased from 94.04 +/- 39.04 to 126.82 +/- 47.36 ml/min (p less than 0.05). The plasma clearance of N-demethyl and N-oxide metabolites were similar for both periods, but the cumulative renal excretion (0 to 96 hours) decreased significantly (p less than 0.01) for period B versus period A. This definite but moderate inductive effect of rifampin on the pharmacokinetics of pefloxacin does not suggest a dose modification of pefloxacin in therapeutic association with rifampin, but pefloxacin assay in plasma seems to be advisable.
authors.affiliation: Hôpital Charles Nicolle, Rouen, France.
authors.forename: G
authors.initials: G
authors.lastname: Humbert
authors.forename: I
authors.initials: I
authors.lastname: Brumpt
authors.forename: G
authors.initials: G
authors.lastname: Montay
authors.forename: A
authors.initials: A
authors.lastname: Le Liboux
authors.forename: A
authors.initials: A
authors.lastname: Frydman
authors.forename: F
authors.initials: F
authors.lastname: Borsa-Lebas
authors.forename: N
authors.initials: N
authors.lastname: Moore
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D006801:Humans; D008297:Male; D015366:Pefloxacin / Q000493:pharmacokinetics*; D012016:Reference Values; D012293:Rifampin / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D015366:Pefloxacin; D012293:Rifampin