Vol.53 No.S-1 July 2005
A dose-finding study on doripenem in chronic respiratory tract infection
1)Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases,
Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa, Japan
2)Department of Respiratory Medicine, Division of Cancer Control,
Institute of Development, Aging and Cancer, Tohoku University
3)Department of Respiratory Diseases, Kanagawa Prefectural Cardiovascular and
Respiratory Diseases Center Hospital (Present: Odagiri Respiratory Disease Clinic)
4)Department of Internal Medicine, Shinrakuen Hospital
5)Division of Respiratory Diseases, Department of Internal Medicine,
Kawasaki Medical School (Present: Kurashiki Daiichi Hospital)
6)Division of Pathogenesis and Disease Control, Department of Infectious Diseases,
Oita University Faculty of Medicine
7)Department of Pharmacology Hamamatsu University School of Medicine
(Present: Hamamatsu Institute of Clinical Pharmacology and Therapeutics)
8)Department of Microbiology, Toho University School of Medicine
9)St. Marianna University School of Medicine
Abstract
A randomized, double-blind, dose-finding study on doripenem (DRPM), a new carbapenem antibiotic for injection, was conducted in patients with chronic respiratory tract infection to evaluate the safety and efficacy at the recommended dose of 250 mg b.i.d. DRPM was also evaluated at a high dose of 500 mg b.i.d. to show that the dose of 250 mg b.i.d. is appropriate therapeutically.
1. Clinical efficacy
Of the 70 patients evaluated for efficacy, 36 took DRPM at the dose of 250 mg b.i.d. Efficacy was 100.0% (36/36) and the 95% confidence interval was 90.3-100.0%. Based on clinical data from currently available carbapenem antibiotics, the expected efficacy of DRPM was calculated at 85% in patients with chronic respiratory tract infection. Actual efficacy was higher than expected efficacy. These results and the precision of efficacy analysis provided the rationale supporting the appropriateness of the dose (250 mg b.i.d.) therapeutically for chronic respiratory tract infection. Efficacy at the high dose of 500 mg b.i.d. was 88.2% (30/34) and no significant difference was seen between two groups.
2. Bacteriological effect
Bacteriological response was assessable in 36 of the 70 patients. Bacterial eradication was 94.1% (16/17) in the 250 mg b.i.d. group and 89.5% (17/19) in the 500 mg b.i.d. group with no significant difference seen between two groups.
3. Safety
The incidence of nonlaboratory adverse drug reactions was 2.6% (1/38) in the 250 mg b.i.d. group and 2.9% (1/34) in the 500 mg b.i.d. group. The incidence of laboratory adverse drug reactions was 28.9% (11/38) in the 250 mg b.i.d. group and 23.5% (8/34) in the 500 mg b.i.d. group with no significant difference between groups.
These results show that DRPM is sufficiently therapeutic and that the dose of 250 mg b.i.d. is appropriate therapeutically for chronic respiratory tract infection.
Key word
doripenem, dose finding trial, bacterial exacerbation, pulmonary diseases, double-blind study
Received
January 11, 2005
Accepted
March 17, 2005
Jpn. J. Chemother. 53 (S-1): 169-184, 2005
