A dose-finding study on doripenem in chronic respiratory tract infection

Atsushi Saito, Akira Watanabe, Shigeki Odagiri, Nobuki Aoki, Toshiharu Matsushima, Masaru Nasu, Mitsuyoshi Nakashima, Keizo Yamaguchi, Jingoro Shimada

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    2 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)169-184
    Number of pages16
    JournalJapanese Journal of Chemotherapy
    Volume53
    Issue numberSUPPL. 1
    Publication statusPublished - 2005 Jul

    Keywords

    • Bacterial exacerbation
    • Doripenem
    • Dose finding trial
    • Double-blind study
    • Pulmonary diseases

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)

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