Vol.53 No.S-1 July 2005
Late phase II study of doripenem in urological infections
Department of Urology, Kobe University, School of Medicine,
7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, Japan
Abstract
We conducted an open-label clinical study to determine the efficacy, safety, and dosage and administration of doripenem (DRPM), a new carbapenem antibiotic for injection, in patients with infection in urology. We also conducted a pharmacokinetic study to determine the distribution of DRPM in prostate tissue.
1. Efficacy
In the open-label clinical study, DRPM was evaluated in one patient with acute uncomplicated pyelonephritis, nine with complicated pyelonephritis, 11 with complicated cystitis, six with acute prostatitis, and five with epididymitis. DRPM was administered at a dose of 250 mg, b.i.d., 250 mg, t.i.d., or 500 mg, b.i.d. for 3 to 14 days. Clinical efficacy judged by attending urologists was 84.4% (27/32), and for the dosage regimen used for the largest cohort of patients (250 mg, b.i.d.) was 87.5% (21/24).
Based on criteria of the Japanese UTI Committee, overall clinical efficacy for complicated urinary tract infection (pyelonephritis, cystitis) was 100.0% (16/16).
Bacteriologically, eradication for 34 bacterial strains (13 gram-positive and 21 gram-negative) isolated prior to initiation of treatment was 97.1%.
2. Pharmacokinetics
In the pharmacokinetic study, DRPM was administered to prostatectomy patients at a single dose of 250 mg or 500 mg. Blood and prostate tissue samples were collected within 60 to 160 minutes of the start of administration. Prostate tissue concentration was 0.76-2.23 μg/g in the 250 mg group and 1.04-4.51 μg/g in the 500 mg group.
3. Safety
In the open-label clinical study, adverse drug reactions (symptoms) occurred in three of 40 patients (7.5%) and adverse drug reactions (abnormal laboratory findings) in eight of 39 (20.5%). In the pharmacokinetic study, adverse drug reactions (abnormal laboratory findings) occurred in one of 12 patients (8.3%), with no adverse drug reactions (symptoms) reported in any of the 13 patients. No serious or clinically significant event was reported in either study.
These results suggest that DRPM is well distributed in prostate tissue and useful for urological infection treatment.
Key word
doripenem, late phase II study, pyelonephritis, complication, cystitis
Received
January 11, 2005
Accepted
February 24, 2005
Jpn. J. Chemother. 53 (S-1): 216-229, 2005
