FUNDAMENTAL AND CLINICAL STUDIES ON BRL25000 (CLAVULANIC ACID-AMOXICILLIN) IN INTERNAL FIELD

• Published in: CHEMOTHERAPY Vol. 30; no. Supplement2; pp. 152 - 167
• Main Author: TAKEBE, KAZUO
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1982
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.30.Supplement2_152

Minimum inhibitory concentrations (MICs) of BRL25000 against 51 strains of clinically isolated β-lactamase producing coagulase negative Staphylococcus were determined, as were MICs for amoxicillin (AMPC) against the same organisms. The MIC of BRL25000 was less than half that of AMPC for 47 of the 51 strains (92.2%). For 27 of the 51 strains (52.9%) the MIC of BRL25000 was less than 6.25μg/ml. A single dose of 375 mg of BRL25000 was administered orally to 5 healthy male adults at times of fasting and non-fasting. At fasting, the peak plasma levels were 2.90μg/ml (1.5 hours) for AMPC and 1.91μg/ml (1.0 hour) for clavulanic acid (CVA). The peak urinary levels detected were 269.4μg/ml (2-4 hours) for AMPC and 94.8μg/ml (0-2 hours) for CVA. Urinary recovery rates during the first 6 hours averaged 66.0% and 32.8% for AMPC and CVA respectively. Non-fasting peak plasma levels were 3. 25μg/ml (1.5 hours) for AMPC and 1.89μg/ml (1.5 hours) for CVA and the peak urinary levels were 462.2μg/ml (0-2 hours) for AMPC and 131.6μg/ml (0-2 hours) for CVA. Urinary recovery rates during the first 6 hours averaged 49.5% for AMPC and 29.0% for CVA. BRL25000 was administered to 44 patients with respiratory tract infections (RTI) and urinary tract infections (UTI). Individual doses of 375mg were administered either 3 or 4 times per day. The overall efficacy was evaluated as 84.1%, being 85.7% and 83.8% for RTI and UTI respectively. The clinical efficacy in UTI caused by AMPC-resistant bacteria was assessed by isolated bacterial, as follows; E. coli (92.9%, 14 cases), K. pneumoniae (50%, 4 cases) and K. oxytoca (100%, 1 case). The clinical efficacy in UTI caused by AMPC-resistant bacteria, assessed by individual disease was as follows; acute cystitis (100.0%, 7 cases), acute pyelonephritis (100.0%, 3 cases), chronic cystitis (75.0%, 4 cases), chronic pyelonephritis (100.0%, 2 cases) and complicated UTI (25.0%, 4 cases). The side effects were observed 3 cases of diarrhea, 1 of rash, 1 of nausea and 1 of dizziness. However, no laboratory abnormalities were found.