Cefamandoleに関する基礎的・臨床的研究 BASIC AND CLINICAL STUDIES ON CEFAMANDOLE
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新Cephalosporin系抗生物質であるCefamandoleについて基礎的・臨床的検討を行なった。<BR>CefamandoleはCEZ, CFX, CET, CERなど他のCephalosporin系抗生剤と比べて, <I>E. coli. Proteus mimbilis</I>に対し特に優れめ抗菌力を示し, ラットでの臓器内不活性化も少なく, 十分な臓器内濃度, 胆汁中排泄が得られた。<BR>Cefamandoleの1回1～2gを1日2～3回点滴あるいは静注で臨床例8例 (肺炎2例, 胆道感染2例, 尿路感染2例。副鼻腔炎1例, 腹膜炎1例) に使用し, 効果不明例および不適当例を除くと6例中4例に有効 (有効率67%) であった。副作用ないし臨床検査異常値としては好酸球増多 (1%-11%) 1例のみであった。
Cefamandole sodium (CMD), a newly synthesized cephalosporin antibiotics, was examined on its <I>in vitro</I> activity against bacteria isolated from human infection foci, serum levels and urinary excretion rates in human, tissue concentrations in rats, serum and bile levels and biliary excretion rates in rabbits as well as its effectiveness in clinical cases. The results obtained were as follows:<BR>1) Antibacterial activity:<BR>CMD was found to be more active against most of <I>E. coli</I> and <I>P. mirabilis</I> strains than cephalothin (CET), cefazolin (CEZ), cephaloridine (CER) and cefoxitin (CFX). Against <I>S. aureus</I>, CMD was found to be similarly active to CEZ, more active than CFX, and less active than CET and CER, although most of <I>P. vulgaris</I> and <I>P. rettgeri</I> strains were highly resistant to CMD.<BR>2) Serum level and urinary excretion (human):<BR>The peak serum level of CMD in a patient with liver cirrhosis was found to be 86μg/ml at 15 min. after single intravenous injection of 1 g and the serum levels descended thereafter as follows; 30 min. 68μg/ml; 60 min. 49μg/ml; 120 min. 28.6μg/ml; 240 min. 3.2μg/ml; 360 min. 0.84μ/ml. The urinary excretion rate was 52% in 6 hours after administration.<BR>3) Organ distribution (rats):<BR>The highest tissue concentrations of CMD after intramuscular administration of 100 mg/kg were found in kidneys, followed by liver, serum, lungs, muscles, spleen and brain. This distribution pattern was similar to that of CEZ and CFX. The peak levels of CMD in kidney, liver, serum and lungs were higher than those of CEZ and lower than those of CFX. The descent of CMD tissue concentrations was more gradual than that of CFX and steeper than that of CEZ. No remarkable inactivation of CMD mixed with rat organ homogenates was observed after overnight storage in a icebox.<BR>4) Biliary excretion (rabbits): Concentrations of CMD in the bile of rabbits collected through choledochus canula was estimated at 10 min. intervals after an intravenous injection of 50 mg/kg. Markedly higher (4-5 times) concentrations were found in the bile than in the sera throughout the 3 hr. course of the experiment. The total biliary recovery of CMD in 3 hrs. reached up to 1.2-1.4% of the dose. Comparing these findings with those formerly obtained about CEZ and CER, the biliary excretion of CMD was similar to that of CEZ, while that of CER was much lower than them.<BR>5) Clinical trials; Eight clinical cases (pneumonia 2, biliary tract infection 2, U. T. I. 2, sinusitis 1, peritonitis 1) were treated with CMD 1-2g/day by intravenous injection or drip infusion. Excepting two drop out cases (one pneumonia case died of heart failure, another sinusitis case discharging <I>P. aeruginosa</I>) four out of six cases favorably responded to the treatment. No side effects were observed, although one case showed temporary eosinophilia (11%).
CHEMOTHERAPY 27(Supplement5), 260-271, 1979
Japanese Society of Chemotherapy