Fillastre J P, Ings R M, Leroy A, Humbert G, Godin M
Nouv Presse Med. 1981 Feb 26;10(8):574-9.
The pharmacokinetics of cefotaxime were investigated in 6 healthy subjects and in 22 uraemic patients with various degrees of renal insufficiency. After i.v. bolus injection of a single 15 mg/kg dose, pharmacokinetic data were calculated using a two compartment model. Serum and urine concentrations were determined by microbiological (M.A.) and HPLC assays. With microbiological assay, the elimination serum half-life (T 1/2) increased in patients according to their degree of renal insufficiency and reached 10 hours when creatinine clearance fell below 10 ml.min-1. When concentrations of cefotaxime and its derivatives (desacetyl cefotaxime, M2 and M3) were determined by HPLC assay, the elimination serum half-life of cefotaxime (T 1/2) was not modified in severe uraemic patients; however the elimination half-life of the metabolites increased when creatinine clearance decreased. Cefotaxime can be administered at a dose of 1 g i.v., twice daily in patients with stable chronic renal insufficiency when creatinine clearance is above 5 ml min-1. In cases of more severe renal failure, the dose should be halved and given i.v. every 12 hours.
在6名健康受试者和22名不同程度肾功能不全的尿毒症患者中研究了头孢噻肟的药代动力学。静脉推注单次15mg/kg剂量后，使用二室模型计算药代动力学数据。血清和尿液浓度通过微生物学（M.A.）和HPLC测定法测定。采用微生物学测定法时，患者的血清消除半衰期（T 1/2）根据肾功能不全程度增加，当肌酐清除率低于10ml.min-1时达到10小时。当通过HPLC测定法测定头孢噻肟及其衍生物（去乙酰头孢噻肟、M2和M3）的浓度时，重度尿毒症患者中头孢噻肟的血清消除半衰期（T 1/2）未改变；然而，当肌酐清除率降低时，代谢物的消除半衰期增加。当肌酐清除率高于5ml.min-1时，稳定的慢性肾功能不全患者可以静脉注射1g剂量的头孢噻肟，每日两次。在更严重的肾衰竭病例中，剂量应减半并每12小时静脉注射一次。
