Influence of rifampin on the pharmacokinetics of pefloxacin

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 < 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 < 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 < 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. Clinical Pharmacology and Therapeutics (1991) 50 , 682–687; doi: 10.1038/clpt.1991.207