EFFECTS OF DU-6859A, A NEW QUINOLONE ANTIMICROBIAL, ON THEOPHYLLINE METABOLISM IN IN-VITRO AND IN-VIVO STUDIES

In vitro and in vivo studies were conducted to investigate the drug in teraction between a new quinolone antimicrobial, DU-6859a, and theophy lline (TP). The effect of DU-6859a on TP metabolism was evaluated in v itro by measuring the rate of TP metabolite formation by using human l iver microsomes. DU-6859a inhibited the metabolism of TP, especially t he formation of 1-methylxanthine, in vitro, but to a lesser extent tha n other drugs that are known to interact with TP. TP was administered alone (200 mg twice a day [b.i.d.] for 9 days) or in combination with DU-6859a (50 or 100 mg b.i.d. for 5 days) to six healthy subjects. DU- 6859a administered at a dose of 50 mg resulted in no changes in serum TP concentrations, and slight increases in serum TP concentrations wer e observed at a dose of 100 mg. Moreover, the administration of 100 mg of DU-6859a resulted in decreases in all urinary TP metabolites, with significant differences. It appears that although DU-6859a has a weak inhibitory effect on TP metabolism in vitro, its concomitant use,vith TP at clinical dosage levels does not cause any adverse effects, show ing only a slight in.crease in blood TP concentrations and a decrease in urinary metabolites.