Vol.53 No.S-1 July 2005
Early phase II study of doripenem, a new carbapenem antibiotic for injection
1)Institute of Medical Science, St. Marianna University School of Medicine,
2-16-1 Sugao Miyamae-ku, Kawasaki, Kanagawa, Japan
2)Department of Microbiology, Toho University School of Medicine
3)Department of Internal Medicine (Department of Infection Control), Jikei University
4)Faculty of Medicine, University of the Ryukyus
5)Kobe University, School of Medicine
6)Tokyo Metropolitan Geriatric Medical Center
Abstract
A multicenter prospective early phase II study was conducted at 41 sites in Japan in patients with internal and urologic infection to evaluate the dosage and administration of doripenem (DRPM), a new carbapenem antibiotic for injection, and to assess its safety and efficacy.
Subjects numbered 106, of whom 75 (internal medicine: 41, urology: 34) were evaluated for efficacy, 105 for safety in abnormal laboratory test findings, and 106 in abnormal symptoms. The usefulness of DRPM in 75 was evaluated and DRPM concentration in the sputum determined in 5.
DRPM was administered intravenously for 30 to 60 minutes at 125 mg b. i. d., 250 mg b. i. d., 250 mg t. i. d., and 500 mg b. i. d., with the following results:
Efficacy was 95.1% (39/41) in internal medicine patients and 97.1% (33/34) in urology patients, for an overall efficacy of 96.0% (72/75). Bacterial eradication was 86.4% (19/22) in internal medicine patients and 97.1% (33/34) in urology patients, for an overall bacterial eradication of 92.9% (52/56).
In safety, adverse drug reactions (symptoms) observed in 3 patients (3 events: tongue numbness, headache, and rash) were not serious and disappeared after completion of treatment. Adverse drug reactions (abnormal laboratory test findings) observed in 25 patients (45 events) included increased GPT (11 cases), GOT (6 cases), and eosinophilia (7 cases), all of which were slight and improved or returned to normal after completion of treatment. Overall safety was 98.1% (103/105).
Of the 75 patients evaluated for DRPM usefulness, usefulness rate 92.9% (39/42) in internal medicine patients and 93.9% (31/33) in urology patients, for an overall usefulness of 93.3% (70/75).
These results show that DRPM has the expected efficacy without adverse drug reactions that might raise clinical issues, so DRPM is expected to produce sufficient therapeutic effect in treating target infection.
Key word
carbapenem, doripenem, respiratory tract infection, urinary tract infection, early phase II clinical study
Received
January 11, 2005
Accepted
March 17, 2005
Jpn. J. Chemother. 53 (S-1): 143-156, 2005
