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 interaction between a new quinolone antimicrobial, DU-6859a, and theophylline (TP). The effect of DU-6859a on TP metabolism was evaluated in vitro by measuring the rate of TP metabolite formation by using human liver microsomes. DU-6859a inhibited the metabolism of TP, especially the formation of 1-methylxanthine, in vitro, but to a lesser extent than 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 were 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 with TP at clinical dosage levels does not cause any adverse effects, showing only a slight increase in blood TP concentrations and a decrease in urinary metabolites.
Niki
Y
Y
Department of Medicine, Kawasaki Medical School, Kurashiki, Japan.
Itokawa
K
K
Okazaki
O
O
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D024841:Fluoroquinolones; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013806:Theophylline / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C076246:sitafloxacin; D013806:Theophylline