CLINICAL PHASE-I STUDY OF CARUMONAM

• Published in: CHEMOTHERAPY Vol. 35; no. Supplement2; pp. 216 - 233
• Main Authors: NAKAMURA, NOBUTO, OHBA, YASUHIRO, NANNO, TATSUO, YAMAMOTO, TOSHIO, ADACHI, YUKIHIKO, SUWA, MASAO, INOUE, HIROSHI, NAGAMINE, YASUROH, ENOMOTO, MASAKAZU
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Chemotherapy 1987; 公益社団法人 日本化学療法学会
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.35.Supplement2_216

A clinical phase-I study of carumonam (CRMN, AMA-1080/Ro 17-2301) was carried out in 27 healthy male adult volunteers to study the safety and pharmacokinetics of the drug. Administration of CRMN was performed in the following order: in single-dose studies, starting from 500mg intravenous drip infusion (i.v.d.), 1, 000mg i.v.d., 1, 000mg intramuscular injection (i.m.), 1, 000mg i. v. injection and 2, 000mg i.v.d., and in the repeated-dose studies, two i.v. doses of 2, 000mg in 1 day, five i.v. doses of 2, 000mg in 3 days and eleven i.v. doses of 2, 000mg in 6 days. The results were as follows: 1) In the couse of the first injection, in the 5 i.v. dose study, 1 of 3 subjects complained of nausea, which disappeared immediately after termination of the injection. This subject showed no abnormalities after the second injection. No abnormalities attributable to CRMN were observed in subjective or objective symptoms, or in the physical tests. 2) No abnormalities attributable to CRMN were observed in the laboratory tests, except for a slight elevation of GPT in 1 of 6 subjects given 11 i.v. doses of 2, 000mg. 3) As to fecal bacterial flora, a reversible change in aerobes, i.e. decrease in Enterobacteriaceae and increase in enterococci, was observed, while anaerobes were less affected. C. dificile, thought to be a cause of antibiotic-associated colitis, was not detected in any of the subjects. 4) The half-life of CRMN was 1.4-1.6 hrs by i. v. administration. Its serum level reached a peak 0.7h after i.m. administration and reduced with a half-life of 2.0h. The 24h urinary recovery rate of CRMN was 63% to 76% of the doses, most of which was excreted unmodified within 7.5h after administration. The half-life of CRMN when administered at 2, 000mg as a series of 11 i.v. doses was 1.5h at the first dose and 1.4h at the final dose, suggesting no influence by the serial administration. 5) No active metabolites were detected in urine, although a small amount of open β-lactam ring metabolite without antibiotic activity was detected in urine. From the above findings, we conclude that CRMN is well tolerated in healthy subjects and applicable for further clinical evaluation in patients.