CURRENT THERAPEUTIC RESEARCH ® VOL.58, NO. 4, APRIL1997 INFLUENCE OF CIPROFLOXACIN ON PHARMACOKINETICS OF RIFAMPIN RATINDERJHAJ,1 ASHUTOSH ROY, 2 ROMAUPPAL, 1 AND DIGAMBAR BEHERA 2 1Departments of Pharrnacology and 2pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India ABSTRACT The pharmacokinetics of oral rifampin was studied in rabbits (24 mg/kg per day) as well as in humans (450 mg/d) who were taking antituberculosis medicine, after concurrent ciprofloxacin adminis- tration for a minimum of 5 days. There were no significant changes in the maximum plasma concentration (Cm~), time at Cm~, area under the plasma concentration-time curve, or elimination half-life of rifampin after ciprofloxacin coadministration in rabbits or hu- mans. Key words: fluoroquinolones, pharmacokinetics, interac- tions, antibiotics. INTRODUCTION Fluoroquinolones inhibit theophylline and caffeine metabolism by the in- hibition of a specific isozyme of cytochrome P-450 (CYPIA2). 1 Data on the effects of quinolones on cytochrome isozymes involved in the metabolism of other drugs is sparse. Although rifampin is known to induce the production of specific cytochrome P-450 isozymes (CYP2C9, CYP2D6, CYP3A3, and CYP3A4), at least one study in rabbits has reported an increase in cipro- floxacin clearance after multiple-dose administration of rifampin for 6 days. 2 This raises the possibility of a common cytochrome P-450 isozyme being affected by both drugs. Rifampin and fluoroquinolones are increas- ingly being coadministered for the treatment of a number of resistant infections (eg, in infections with Mycobacterium tuberculosis, 3 Mycobacte- rium leprae, 4 atypical mycobacteria, 5 methicillin-resistant Staphylococcus aureus, 6'7 and Pseudomonas aeruginosaS), often for long periods of time. The propensity for their concurrent use prompted us to study the effects of ciprofloxacin on rifampin kinetics in rabbits and humans. Cipro- floxacin was coadministered with rifampin after pretreatment with ri- fampin alone for a minimum of 10 days in rabbits, or 15 days in humans. This pretreatment period was included to allow for maximal autoinduction of the metabolizing enzymes by rifampin, a process that has been shown to be completed in 6 to 7 days. 9'1° Addresscorrespondence to: R.Uppal,DM,Department of Pharmacology, Postgraduate Instituteof Medical Educationand Research,Chandigarh,India, 160012. Receivedfor publication on December 3, 1996. Printedin the U.S.A. Reproduction in whole or part is not permitted. 260 0011-393X/97/$3.50