肾功能不全患者单次和多次短时间静脉输注林西多明的药代动力学。

J Sennesael, D Verbeelen, S Degré, P Unger, J C Stolear, J Ostrowski, H M von Hattingberg, W Gaertner
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引用次数: 0

摘要

对两组冠心病(CHD)患者单次和多次给药2mg林西多明(sin1)后进行药代动力学测定。12例伴有肾功能不全的冠心病患者(RI组,Clcr: 11 +/- 6 ml/min)和12例肾功能正常的冠心病患者(对照组,Clcr: 88 +/- 22 ml/min)采用短时间静脉输注林西多明。总sin1c (sin1 + sin1c)的血浆浓度时间过程的测量被发现适合于估计终末相的sin1c相关半衰期(t50% = 1.5 +/- 0.5 h),因为sin1从血浆中迅速消除(t50% = 12至20分钟)。此外,在单次和多次给药后,平均总sin1c血浆谱相等,这表明肾病患者在重复给药期间,sin1c不会累积。ri组患者sin1c总排泄平均最大肾分数(fe = 0.8 +/-剂量的0.8%)与对照组相应的平均值(fe(N) = 5.8 +/-剂量的5.1%)有显著差异。第1天与第4天fe和fe(N)无显著差异。由于sin1在血浆中降解非常迅速,并且sin1c主要通过体外清除,因此对于合并肾功能衰竭的冠心病患者,不应考虑任何关于重复sin1给药方案的限制。
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Pharmacokinetics of linsidomine (SIN 1) after single and multiple intravenous short infusions in patients with renal insufficiency.

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.

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