Barriere S L, Gambertoglio J G, Lin E T, Conte J E
Antimicrob Agents Chemother. 1982 Jan;21(1):54-7. doi: 10.1128/AAC.21.1.54.
The pharmacokinetics of amdinocillin (mecillinam) after multiple intravenous doses to healthy subjects are described. Assay of plasma and urine samples was carried out with a sensitive and specific high-pressure liquid chromatographic technique. A dose of 10 mg/kg of body weight was administered every 4 h for six doses. No accumulation was noted. Mean peak plasma concentrations were approximately 50 micrograms/ml, and the plasma half-life was approximately 53 min. Total plasma clearance was 4.6 ml/min per kg after the first dose, which declined slightly to 4.1 ml/min per kg after the last dose. Renal clearance remained fairly constant at approximately 2.9 ml/min per kg, or twice the creatinine clearance. The fraction excreted unchanged totaled 63% during the 4-h interval after the first dose and was nearly 70% overall. The steady-state volume of distribution was calculated to be 0.26 liter/kg. Urinary concentrations of amdinocillin were far in excess of the usual inhibitory concentrations for susceptible pathogens and were as high as 3,000 micrograms/ml. Dose of amdinocillin every 4 h provide plasma and urine concentrations which should be effective for the treatment of infections.
本文描述了健康受试者多次静脉注射氨比西林（美西林）后的药代动力学。采用灵敏且特异的高压液相色谱技术对血浆和尿液样本进行分析。每4小时给予10mg/kg体重的剂量，共给药6次。未观察到药物蓄积。平均血浆峰浓度约为50μg/ml，血浆半衰期约为53分钟。首剂后总血浆清除率为4.6ml/（min·kg），末次给药后略有下降，至4.1ml/（min·kg）。肾脏清除率相当恒定，约为2.9ml/（min·kg），为肌酐清除率的两倍。首剂后4小时内原形药物排泄分数总计63%，总体接近70%。稳态分布容积经计算为0.26L/kg。氨比西林的尿浓度远远超过对敏感病原体的通常抑制浓度，高达3000μg/ml。每4小时给予氨比西林剂量可使血浆和尿液浓度达到对感染治疗有效的水平。
