Early phase II study of doripenem, a new carbapenem antibiotic for injection

• Published in: Japanese Journal of Chemotherapy Vol. 53; no. Supplement1; pp. 143 - 156
• Main Authors: Shimada, Jingoro, Shiba, Kohya, Yamaguchi, Keizo, Kamidono, Sadao, Saito, Atsushi, Inamatsu, Takeshi
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 2005; 公益社団法人 日本化学療法学会
• Subjects: carbapenem; doripenem; early phase II clinical study; respiratory tract infection; urinary tract infection
• ISSN: 1340-7007; 1884-5886
• DOI: 10.11250/chemotherapy1995.53.Supplement1_143

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 125mg b.i.d., 250mg b.i.d., 250mg t. i. d., and 500mg 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.