CLINICAL RESULTS ON BRL 28500 (CLAVULANIC ACID-TICARCILLIN) FOR VARIOUS INFECTIONS IN THE FIELD OF SURGERY

• Published in: CHEMOTHERAPY Vol. 34; no. Supplement4; pp. 818 - 832
• Main Authors: SAKAI, KATSUJI, FUJIMOTO, MIKIO, UEDA, TAKAMI, MITSUYOSHI, HIJIRI, DOI, SUSUMU, MAEDA, SADAKUNI, SASAKI, TAKEYA, MORIMOTO, YUZURU, SAWADA, AKIRA, MASADA, AKINORI
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Chemotherapy 1986
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.34.Supplement4_818

BRL 28500 is an injectable antibiotic formulation of ticarcillin (TIPC) as the disodium salt and clavulanic acid (CVA) as the potassium salt in the ratio of 15 parts to 1 part. The formulation with the β-lactamase inhibitor CVA is intended to broaden the antibacterial spectrum of TIPC to additionally encompass many β-lactamase producing bacteria. When BRL 28500 (3.2 g) was administered to 3 normal adults by drip infusion over 30 minutes, the mean blood levels of TIPC and CVA achieved at the end of the administration were 329.1μg/ml and 16.2μg/ml respectively. Urinary excretion in the 6 hours following dosing were 78.3% for TIPC and 61.2% for CVA of the administered dose. Transfer to the exudate was detectable 1 hour after the commencement of dosing with TIPC concentrations increasing gradually to peak at 36.9μg/ml at 5-6 hours. However CVA concentrations were no higher than 0.4-0.8μg/ml. Although biliary excretion differed somewhat between subjects, concentrations of TIPC achieved in the bile of one subject showed a biphasic pattern with at peak of 192.9μg/ml at 1-2 hours and a second peak of 168.9μg/ml at 4-5 hours. Similarly for CVA, peaks of 2.7μg/ml and 1.6μg/ml were found at 1-2 hours and 4-5 hours respectively. In another subject, the bile concentrations reached 107.8μg/ml TIPC and 3.3μg/ml CVA at 1-2 hours. BRL 28500 was also administered to 23 patients with surgical infections. Clinical assessment was rated excellent in 8, good in 8, fair in 3 and poor in 4, giving an overall efficacy rate of 69.6%. By disease, BRL 28500 was found to be effective in 4 out of 5 cases of cholangitis, 4 of 6 cases of postoperative intraperitoneal infection, 2 of 3 cases of peritonitis, 4 of 4 cases of traumatic infections and 2 of 2 cases of other disease. Side effects were observed in none of the cases treated and abnormal laboratory examination values were limited to eosinophilia in 1 case and mild increases of GOT and GPT in 2 cases.