Effect of trovafloxacin, a new fluoroquinolone antibiotic, on the steady-state pharmacokinetics of theophylline in healthy volunteers

Some fluoroquinolone antibiotics interfere with theophylline clearance, thereby raising concentrations of circulating theophylline and increasing the potential for toxicity. The effect of steady-state serum concentrations of the new fluoroquinolone trovafloxacin on the steady-state pharmacokinetics of theophylline was examined in 12 healthy male volunteers. For 7 days, the subjects received morning and evening theophylline doses adjusted to achieve steady-state plasma concentrations of 8-15 mg/L, the lower end of the therapeutic range. From day 8 to day 15, six volunteers received, in addition to theophylline, 200 mg of trovafloxacin in the morning and placebo in the evening (group A) and six received placebo twice daily (group B). Serial plasma samples obtained over 12 h and 60 h after the morning theophylline dose on days 7 and 14, respectively, were analysed for theophylline by HPLC with UV detection. There were no significant differences in mean C-max or AUC(0-12) between the two groups on day 7 or on day 14, nor were there significant within-group differences on the two days. On day 14, mean C-max, AUC(0-12) and T-1/2 (measured on day 14 only) in group A were 10.15 mg/L, 107.32 mg.h/L and 9.0 h, respectively. In group B, the values were 10.81 mg/L, 113.73 mg.h/L and 8.3 h, respectively. The study drugs were well tolerated, and no clinically significant changes in vital signs or laboratory test values were noted. We conclude that steady-state concentrations of trovafloxacin have no clinically significant effect on the steady-state concentrations of theophylline within the therapeutic range in healthy subjects.