Gambertoglio J G, Barriere S L, Lin E T, Conte J E
Antimicrob Agents Chemother. 1980 Dec;18(6):952-6. doi: 10.1128/AAC.18.6.952.
Mecillinam is an amidino penicillinate derivative with a broad spectrum of activity against many gram-negative bacilli. Moreover, marked in vitro synergy against these organisms occurs when mecillinam is combined with other beta-lactam antibiotics. The purpose of this study was to determine the pharmacokinetic disposition of this antibiotic. A single dose of 10 mg/kg was administered to 12 healthy volunteers as a 15-min intravenous infusion. Multiple plasma and urine samples were collected at frequent intervals for 8 and 24 h, respectively. Plasma samples were assayed for mecillinam by using a specific high-pressure liquid chromatographic assay developed in our laboratory. Peak plasma levels ranged from 34 to 80 micrograms/ml, and after 4 h, plasma levels were 0.7 to 1.9 microgram/ml. The mean terminal plasma half-life was 51.1 +/- 8.6 min. The mean steady-state volume of distribution was calculated to be 0.23 +/- 0.04 liter/kg. The mean plasma and renal clearances were 3.5 +/- 0.4 and 2.5 +/- 0.4 ml/min per kg, respectively. The mean percentage of the dose excreted unchanged in the urine at 4 h was 67 +/- 5%; 71 +/- 6% was recovered in 24 h. Urine concentrations at 4 h were far above the minimum inhibitory concentration for susceptible gram-negative organisms.
美西林是一种脒基青霉素酸盐衍生物，对多种革兰氏阴性杆菌具有广谱活性。此外，当美西林与其他β-内酰胺类抗生素联合使用时，对这些微生物会产生显著的体外协同作用。本研究的目的是确定这种抗生素的药代动力学特征。对12名健康志愿者以15分钟静脉输注的方式给予10mg/kg的单剂量药物。分别在8小时和24小时内频繁采集多个血浆和尿液样本。使用我们实验室开发的特定高压液相色谱法测定血浆样本中的美西林。血浆峰值水平在34至80微克/毫升之间，4小时后，血浆水平为0.7至1.9微克/毫升。平均终末血浆半衰期为51.1±8.6分钟。计算得出平均稳态分布容积为0.23±0.04升/千克。平均血浆清除率和肾脏清除率分别为3.5±0.4和2.5±0.4毫升/分钟/千克。4小时时尿液中以原形排泄的药物剂量平均百分比为67±5%；24小时内回收率为71±6%。4小时时尿液浓度远高于敏感革兰氏阴性菌的最低抑菌浓度。
