Vol.53 No.S-1 July 2005
A dose-finding study of doripenem in patients with complicated urinary tract infection
1)Department of Urology, Kobe University, School of Medicine,
7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, Japan
2)Department of Urology, Okayama University Medical School
3)Department of Urology, Faculty of Medicine, Kyushu University
(Present: Department of Urology, University of Occupational and Environmental Health)
4)Department of Pharmacology, Hamamatsu University, School of Medicine
(Present: Hamamatsu Institute of Clinical Pharmacology and Therapeutics)
5)Kobe University, School of Medicine, Faculty of Health Sciences
6)St. Marianna University School of Medicine
Abstract
We conducted a dose finding study of doripenem (DRPM), a new carbapenem antibiotic for injection, in patients with complicated urinary tract infections to evaluate the safety and efficacy of DRPM at the recommended dose of 250 mg b.i.d. (250 mg group). DRPM was also evaluated at a high dose of 500 mg b.i.d. (500 mg group) to show that the dose of 250 mg b.i.d. is appropriate therapeutically.
Subjects were inpatients aged between 20 and 79 years shown to have pyuria of at least 5 WBCs/hpf and bacteriuria of at least 104 CFU/mL. In patients with previous prostatic resection, an interval of more than 6 months after surgery was required for inclusion. Patients with indwelling catheters were excluded.
Overall efficacy (primary endpoint) was 97.4% (37/38) in the 250 mg group and the 95% confidence interval was 86.2% to 99.9%. This efficacy was not below the minimuml 95% confidence interval (78.6%-98.3%) for expected efficacy (90%) and was still higher than expected efficacy. In the 500 mg group, overall efficacy was 96.9% (31/32) and no significant difference was seen between groups.
For secondary endpoints, no significant difference was seen between groups: 1) effect on pyuria was 60.5% in the 250 mg group and 75.0% in the 500 mg group, 2) effect on bacteriuria was 94.7% in the 250 mg group and 84.4% in the 500 mg group, 3) bacteriological response was 95.7% in the 250 mg group and 97.7% in the 500 mg group, and 4) clinical efficacy judged by attending urologists was 94.7% in the 250 mg group and 84.4% in the 500 mg group. These results showed that efficacy at 250 mg b.i.d. was equivalent to that at 500 mg b.i.d..
For safety, the incidence of adverse drug reactions (symptoms) was 4.9% in the 250 mg group and 2.9% in the 500 mg group, respectively, and the incidence of adverse drug reactions (abnormal laboratory findings) 15.4% and 15.2%, with no significant difference seen between groups in either case.
Considering overall efficacy in the 250 mg group (still higher than expected efficacy) and the precision of efficacy analysis, this study showed that DRPM at 250 mg b.i.d. is appropriate as a therapeutic dose for patients with complicated urinary tract infection.
Key word
doripenem, complication, urinary tract infection, clinical efficacy, dose finding trial
Received
January 11, 2005
Accepted
February 24, 2005
Jpn. J. Chemother. 53 (S-1): 230-243, 2005
