Novak E, Lakings D B, Paxton L M
Upjohn Company, Kalamazoo, Michigan 49007, USA.
Antimicrob Agents Chemother. 1987 Nov;31(11):1706-10. doi: 10.1128/AAC.31.11.1706.
Cefpimizole sodium (AC-1370, U-63196E) was administered intramuscularly in doses from 100 mg (0.5 ml) to 2,000 mg (two 3.5-ml doses) to healthy human volunteers in three double-blind placebo and positive-controlled (cefotaxime, cephalothin) single-dose studies and in two multiple-dose studies. Mild transient pain was observed at the injection site, but no erythema, petechia, necrosis, or atrophy was noted. Creatinine phosphokinase values were increased during the study in the cefpimizole- and placebo-treated groups but began to return to normal toward the end of the study period (day 5). They were not paralleled by a similar magnitude of elevation in serum glutamic oxalacetic transaminase and lactate dehydrogenase or by pain and tenderness. There were no clinically meaningful or statistically significant changes (P greater than 0.5) or trends in vital signs and no other patterns of drug-related clinical abnormalities noted in any of the laboratory measurements evaluated (hematology, chemistry, urinalysis). No serious side effects occurred during or after the study. Cefpimizole was well tolerated locally and systemically by all the subjects at all administered dosage levels. Cefpimizole concentrations in serum (microbiological assay) remained above 1 microgram/ml at 12 h after drug administration for all dose levels. The median peak concentrations in plasma for the 500- and 1,000-mg twice-daily dosages of cefpimizole were, respectively, 21.6 and 45.5 micrograms/ml on day 1, 16.2 and 43.7 micrograms/ml on day 3, and 20.1 and 41.4 micrograms/ml on day 6 of the study. The apparent terminal disposition half-life throughout the study was about 2.0 h. The median amounts of cefpimizole excreted in the urine for the first 12 h of each day evaluated were 370 and 1,071 mg on day 1, 416 and 972 mg on day 3, and 370 and 975 mg on day 6 for the 500- and 1,000-mg twice-daily dosages, respectively. Dose proportionally of cefpimizole was obtained for the 500- and 1,000-mg and the 2,000-mg groups. The absorption, distribution, and elimination of cefpimizole after multiple-dose intramuscular administration were uniform, were linear in relation to dose, and did not result in drug accumulation.
在三项双盲、安慰剂对照和阳性对照（头孢噻肟、头孢噻吩）单剂量研究以及两项多剂量研究中，对健康人类志愿者肌肉注射头孢咪唑钠（AC - 1370，U - 63196E），剂量从100毫克（0.5毫升）至2000毫克（两剂3.5毫升）。在注射部位观察到轻度短暂疼痛，但未发现红斑、瘀点、坏死或萎缩。在研究期间，头孢咪唑组和安慰剂组的磷酸肌酸激酶值均升高，但在研究期结束时（第5天）开始恢复正常。血清谷草转氨酶和乳酸脱氢酶没有出现类似程度的升高，也没有疼痛和压痛与之平行。生命体征没有出现具有临床意义或统计学显著意义的变化（P大于0.5），在任何评估的实验室测量（血液学、化学、尿液分析）中也未发现其他与药物相关的临床异常模式。研究期间及之后均未发生严重副作用。在所有给药剂量水平下，所有受试者对头孢咪唑的局部和全身耐受性良好。给药后12小时，所有剂量水平的血清头孢咪唑浓度（微生物测定）均保持在1微克/毫升以上。在研究的第1天，头孢咪唑每日两次500毫克和1000毫克剂量的血浆中位峰浓度分别为21.6和45.5微克/毫升，第3天为16.2和43.7微克/毫升，第6天为20.1和41.4微克/毫升。整个研究期间的表观终末处置半衰期约为2.0小时。对于每日两次500毫克和1000毫克剂量，在评估的每天前12小时尿液中排泄的头孢咪唑中位量在第1天分别为370和1071毫克，第3天为416和972毫克，第6天为370和975毫克。500毫克、1000毫克和2000毫克组的头孢咪唑呈剂量比例关系。多次肌肉注射后，头孢咪唑的吸收、分布和消除是均匀的，与剂量呈线性关系，且不会导致药物蓄积。
