Vol.55 No.S-1 October 2007
Concomitant administration study of garenoxacin and theophylline
Department of Clinical Infectious Diseases, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan
Abstract
The effect on the plasma concentration of theophylline when garenoxacin mesilate hydrate(GRNX), a new quinolone antibacterial agent, was administered concomitantly was evaluated in 9 healthy male adult volunteers. Initially 400 mg of theophylline at a daily dose was given orally for 4 days prior to GRNX administration. The plasma concentration of theophylline was determined on day 4 and used as the control level. From day 5, 400 mg of GRNX was given orally once daily in the morning for 7 days with concomitant administration of theophylline at the same dose as above.
The geometric mean Cmax and AUC values of theophylline on day 11 (the 7th day after GRNX administration started) were 1.18 and 1.19 times of the control values. The 90% confidential interval for the ratios of the geometric mean of Cmax was 1.02-1.37 and AUC was 1.03-1.37. On day 8 (the 4th day after GRNX administration started), these parameters were 1.18 and 1.19 times of the control values indicating same values as the day 11. No significant difference was noted in plasma level and/or pharmacokinetic parameters of GRNX between day 8 and day 11.
After GRNX administration started, seven adverse events occurred in five subjects. Side effects were observed in two subjects. Events were diarrhea (2 subjects, 2 events) and abdomen pain (1 subject, 1 event). All events were judged mild and both subjects recovered without treatment.
From the above results, GRNX was considered to increase the plasma level of theophylline by approximately 20% when administered concomitantly. Adjustment of the dosage of GRNX seems unnecessary, but careful monitoring is recommended when high-dose theophylline is administered, e.g., intravenously.
Key word
garenoxacin, theophylline, drug-drug interaction
Received
June 5, 2007
Accepted
July 18, 2007
Jpn. J. Chemother. 55 (S-1): 206-213, 2007
