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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.
Insights
Rifampin significantly alters pefloxacin pharmacokinetics, reducing its plasma levels and half-life. While not necessitating dose changes, monitoring pefloxacin levels is recommended when used with rifampin.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Infectious Diseases
Background:
- Pefloxacin and rifampin are commonly co-administered for deep-seated infections.
- Rifampin is a known inducer of drug metabolism enzymes.
- Understanding drug interactions is crucial for effective antibiotic therapy.
Purpose of the Study:
- To investigate the pharmacokinetic interaction between pefloxacin and rifampin.
- To determine the influence of rifampin on pefloxacin metabolism and elimination.
- To assess the clinical implications for co-therapy.
Main Methods:
- Randomized crossover trial with eight healthy male volunteers.
- Pefloxacin administered alone versus after rifampin induction (900 mg daily for 10 days).
- Pharmacokinetic parameters (plasma concentration, AUC, half-life, clearance) were measured.
Main Results:
- Rifampin significantly decreased pefloxacin's minimum plasma concentration, AUC, and elimination half-life (p < 0.05).
- Plasma clearance of pefloxacin increased significantly (p < 0.05) due to rifampin induction.
- Cumulative renal excretion of pefloxacin metabolites decreased significantly (p < 0.01).
Conclusions:
- Rifampin exhibits a moderate inductive effect on pefloxacin pharmacokinetics.
- The interaction does not currently suggest a need for pefloxacin dose modification.
- Therapeutic drug monitoring of pefloxacin plasma levels is advisable during co-administration with rifampin.