Sennesael J, Verbeelen D, Degré S, Unger P, Stolear J C, Ostrowski J, von Hattingberg H M, Gaertner W
Academisch Ziekenhuis V.U.B., Nefrologie, Brussels, Belgium.
Int J Clin Pharmacol Ther Toxicol. 1993 Nov;31(11):533-41.
Pharmacokinetic measurements were performed in two groups of patients with coronary heart disease (CHD) after single and multiple dosing of 2 mg linsidomine (SIN 1). The drug was administered by intravenous short time infusion in 12 CHD-patients with renal insufficiency (RI group, Clcr: 11 +/- 6 ml/min) and in 12 CHD-patients with normal kidney function (control group, Clcr: 88 +/- 22 ml/min). The measurement of plasma concentration time courses of total SIN 1C (SIN 1 + SIN 1C) was found to be suitable for an estimation of the SIN 1C related half-life of the terminal phase (t50% = 1.5 +/- 0.5 h), as SIN 1 was eliminated from plasma rapidly (t50% = 12 to 20 min). Furthermore, the mean total SIN 1C plasma profiles were equal after single and multiple administration of the drug giving evidence that SIN 1C is not accumulating during repetitive dosing of SIN 1 in patients with renal disease. The mean maximum renal fraction of total SIN 1C excretion of RI-subjects (fe = 0.8 +/- 0.8% of dose) was significantly different from the corresponding mean value of the control group (fe(N) = 5.8 +/- 5.1% of dose). No differences were found for fe and fe(N) between day 1 and day 4. As SIN 1 is degraded in plasma very rapidly and as SIN 1C is cleared mainly extrarenally, any restrictions concerning repetitive SIN 1 dosage regimen should not be considered for CHD-patients with renal failure.
对两组冠心病（CHD）患者单次和多次服用2毫克林西多明（SIN 1）后进行了药代动力学测量。药物通过静脉短时间输注给予12例肾功能不全的冠心病患者（RI组，肌酐清除率：11±6毫升/分钟）和12例肾功能正常的冠心病患者（对照组，肌酐清除率：88±22毫升/分钟）。发现测量总SIN 1C（SIN 1 + SIN 1C）的血浆浓度-时间过程适合估计终末相SIN 1C相关半衰期（t50% = 1.5±0.5小时），因为SIN 1从血浆中快速消除（t50% = 12至20分钟）。此外，单次和多次给药后平均总SIN 1C血浆曲线相同，这表明在肾病患者重复给予SIN 1期间SIN 1C不会蓄积。RI组受试者总SIN 1C排泄的平均最大肾排泄分数（fe =剂量的0.8±0.8%）与对照组相应平均值（fe(N) =剂量的5.8±5.1%）有显著差异。第1天和第4天之间fe和fe(N)未发现差异。由于SIN 1在血浆中降解非常迅速，且SIN 1C主要通过肾外途径清除，对于肾衰竭的冠心病患者不应考虑对重复SIN 1给药方案有任何限制。
