Drusano G L, Standiford H C, Bustamante C, Forrest A, Rivera G, Leslie J, Tatem B, Delaportas D, MacGregor R R, Schimpff S C
Antimicrob Agents Chemother. 1984 Nov;26(5):715-21. doi: 10.1128/AAC.26.5.715.
We characterized the pharmacokinetic profile of imipenem-cilastatin administered intravenously to six normal volunteers in a dose of 1,000 mg of each drug every 6 h for 40 doses. The plasma concentrations of imipenem and cilastatin 1 h after the end of a 30-min infusion were 18.7 (+/- 2.1) and 19.1 (+/- 4.6), 20.0 (+/- 3.2) and 17.8 (+/- 4.8), and 23.4 (+/- 2.3) and 19.1 (+/- 3.5) micrograms/ml in the 1st, 17th, and 37th dosing intervals, respectively. The central compartment volumes of distribution for imipenem and cilastatin were 0.16 (+/- 0.05) and 0.14 (+/- 0.03) liter/kg, respectively. Elimination half-lives were short: 0.93 (+/- 0.09) h for imipenem and 0.84 (+/- 0.11) h for cilastatin. Plasma clearances were 12.1 (+/- 0.06) liters/h per 1.73 m2 for imipenem and 12.4 (+/- 1.1) liters/h per 1.73 m2 for cilastatin. Renal clearance accounted for 54% of the plasma clearance of imipenem and 69% of the plasma clearance of cilastatin. The concentrations of imipenem in plasma and urine remained above the MICs of the vast majority of pathogens throughout the dosing interval.
我们对6名正常志愿者静脉注射亚胺培南-西司他丁的药代动力学特征进行了研究，每种药物剂量为1000mg，每6小时给药1次，共给药40次。在30分钟输注结束后1小时，第1、17和37个给药间隔中亚胺培南和西司他丁的血浆浓度分别为18.7（±2.1）和19.1（±4.6）、20.0（±3.2）和17.8（±4.8）、23.4（±2.3）和19.1（±3.5）μg/ml。亚胺培南和西司他丁的中央室分布容积分别为0.16（±0.05）和0.14（±0.03）升/千克。消除半衰期较短：亚胺培南为0.93（±0.09）小时，西司他丁为0.84（±0.11）小时。亚胺培南的血浆清除率为每1.73m² 12.1（±0.06）升/小时，西司他丁为每1.73m² 12.4（±1.1）升/小时。肾清除率分别占亚胺培南血浆清除率的54%和西司他丁血浆清除率的69%。在整个给药间隔内，血浆和尿液中亚胺培南的浓度均高于绝大多数病原体的最低抑菌浓度。
