Neu H C
Ther Drug Monit. 1981;3(2):121-8. doi: 10.1097/00007691-198102000-00002.
Cefoperazone is a new piperazine cephalosporin derivative which has a broad antibacterial activity against aerobic and anaerobic gram-positive and gram-negative cocci and bacilli, including Pseudomonas aeruginosa. In studies of the intramuscular (i.m.) administration of cefoperazone at doses of 0.25, 0.5, and 1 g, mean peak serum concentrations were 22, 33, and 67 micrograms/ml at 1 hr. At 8 hr, serum levels were 2.1, 4.8, and 5.6 micrograms/ml, respectively, for the three doses. The mean half-life after intramuscular injection was 108-154 min. Urinary recovery ranged from 14 to 18% of an administered dose. Intravenous (i.v.) administration of cefoperazone by rapid (3-5 min) infusion produced serum levels at 15 min of 76, 156, and 244 micrograms/ml after doses of 0.5, 1, and 2 g, respectively. Concentrations of cefoperazone at 8 hr were 2.4, 6.5, and 11.8 micrograms/ml after these respective doses. Serum half-life was 115-120 min and urinary recovery, 29-33%. Levels determined at 5 min after bolus injection were 200 micrograms/ml for 1 g, 275 micrograms/ml for 2 g and 518 micrograms/ml for 3 g. Intravenous infusion studies of cefoperazone in which 2 g of the drug has been infused over 15, 30, or 120 min have yielded levels of 250-260 micrograms/ml. At 12 hr, levels of 1-2 micrograms/ml were still present. The half-life found in these studies ranged from 1.6 to 2.38 hr. Urinary recovery was 25-30%. Serum clearances have been 80-90 ml/min and renal clearances, 18-30 ml/min. The apparent volume of distribution of the compound has ranged from 10 to 16 liters. Comparative studies have shown that cefoperazone produced higher serum levels than cefazolin, cefamandole, cefotaxime, and moxalactam. Biliary concentrations exceed 400 micrograms/ml and are two to four times the levels found with cefazolin or cefamandole. In the presence of renal failure there is a minimal increase in serum half-life; but in the presence of biliary obstruction, serum half-life may reach 11 hr, depending on the degree of biliary obstruction. In the presence of biliary obstruction, the drug is 90% removed from the body by renal excretion.
头孢哌酮是一种新型哌嗪头孢菌素衍生物，对需氧菌和厌氧菌、革兰氏阳性菌和革兰氏阴性球菌及杆菌具有广泛的抗菌活性，包括铜绿假单胞菌。在对头孢哌酮进行0.25克、0.5克和1克剂量的肌内注射研究中，1小时时的平均血清峰值浓度分别为22微克/毫升、33微克/毫升和67微克/毫升。8小时时，这三种剂量的血清水平分别为2.1微克/毫升、4.8微克/毫升和5.6微克/毫升。肌内注射后的平均半衰期为108 - 154分钟。尿液回收率为给药剂量的14%至18%。通过快速（3 - 5分钟）输注静脉注射头孢哌酮，在0.5克、1克和2克剂量后分别于15分钟时产生的血清水平为76微克/毫升、156微克/毫升和244微克/毫升。这些相应剂量后8小时时头孢哌酮的浓度分别为2.4微克/毫升、6.5微克/毫升和11.8微克/毫升。血清半衰期为115 - 120分钟，尿液回收率为29% - 33%。推注注射后5分钟测定的水平，1克剂量为200微克/毫升，2克剂量为275微克/毫升，3克剂量为518微克/毫升。对头孢哌酮进行的静脉输注研究中，2克药物在15分钟、30分钟或120分钟内输注完毕，产生的水平为250 - 260微克/毫升。12小时时，仍存在1 - 2微克/毫升的水平。这些研究中发现的半衰期为1.6至2.38小时。尿液回收率为25% - 30%。血清清除率为80 - 90毫升/分钟，肾脏清除率为18 - 30毫升/分钟。该化合物的表观分布容积为10至16升。比较研究表明，头孢哌酮产生的血清水平高于头孢唑林、头孢孟多、头孢噻肟和莫西沙星。胆汁浓度超过400微克/毫升，是头孢唑林或头孢孟多水平的两到四倍。在肾衰竭情况下，血清半衰期仅有轻微增加；但在存在胆道梗阻时，血清半衰期可能达到11小时，这取决于胆道梗阻的程度。在存在胆道梗阻时，该药物90%通过肾脏排泄从体内清除。
