Effect of quinolone antimicrobials on theophylline pharmacokinetics

The purpose of the research was to ascertain the comparative differences of quinolone antibiotics on theophylline pharmacokinetics. Eight healthy male volunteers were randomly assigned to four treatments. Each was administered norfloxacin (NOR) 800 mg/d, ciprofloxacin (C) 1 g/d, nalidixic acid (NAL) 2 g/d and placebo (P) for 7 days. On the seventh day of each treatment, theophylline (5 mg/kg) iv was administered. The elimination half-life (T 1/2), total body clearance (CL) and volume of distribution at steady state (Vss) of theophylline were calculated using model-independent methods. ANOVA for repeated measures was used for data comparisons. The mean (SD) theophylline results were: CL l/kg/h--NOR .038 (.006), C .033 (.006), NAL .045 (.008), P .044 (.007); T 1/2 h--NOR 9.2 (1.8), C 10.6 (1.8), NAL 8.3 (1.8), P 7.5 (1.4). Theophylline Vss differences by treatment were not significant. NOR and C significantly decreased theophylline's clearance and the clearance change can be of clinical significance.