健康大鼠蛋白质结合亲脂性尿毒症毒素对甲酚的动力学。
文章的细节
-
引用
复制到剪贴板 -
Lesaffer G, De Smet R, D'heuvaert, Belpairea FM, Lameire N, Vanholder R
健康大鼠蛋白质结合亲脂性尿毒症毒素对甲酚的动力学。
生命科学学报，2001,29(4):344 - 344。
- PubMed ID
-
11669466 (PubMed视图］
- 摘要
-
p -甲酚是一种部分亲脂性和蛋白质结合的化合物，与尿毒症中的几种生化改变有关。由于对甲酚动力学从未被研究过，我们研究了它在大鼠体内的动力学行为。结果与肌酐得到的结果进行比较，肌酐是一种水溶性、非蛋白结合的尿毒症潴留溶质，目前被用作尿毒症潴留的标记物。将健康大鼠分为体重相当的3组:(1)对照组(n=6);(2)静脉注射3mg对甲酚的一组(n=7);(3)一组(n=5)接受静脉注射18毫克肌酐。分别于给药后0、5、30、60、120、180和240分钟采血，测定对甲酚和肌酐。每隔1小时收集一次尿液。HPLC法测定对甲酚浓度。对甲酚和肌酐的药代动力学参数由血清浓度-时间曲线采用非室区分析计算。 Each compound showed a concentration at time point 5 min (p-cresol: 6.7 +/- 1.4 mg/L and creatinine: 141 +/- 12 mg/L) which was comparable with values observed in uremic patients; these concentrations decreased gradually towards min 240 (p-cresol: 0.6 +/- 0.3 mg/L and creatinine: 4 +/- 2 mg/L, p<0.05 vs. 5 min in both cases). No p-cresol was found in the serum of control rats and these rats showed no changes in serum concentration of creatinine. Urinary excretions were strikingly different (p-cresol: 23 +/- 10% and creatinine: 95 +/- 25% of the administered dose, p<0.05). The half-life of p-cresol was twice as long as that of creatinine (1.5 +/- 0.8 vs. 0.8 +/- 0.1 h, p<0.05). Total clearance (CLt) was much higher for p-cresol than for creatinine (23.2 +/- 4.5 vs. 8.1 +/- 0.4 mL/min/kg, p<0.01); renal clearance (CLr), however, was substantially lower for p-cresol (4.8 +/- 2.0 vs. 8.2 +/- 1.9 mL/min/kg, p<0.05). Whereas CLt and CLr were similar for creatinine, CLt of p-cresol largely exceeded its CLr (p<0.05). The volume of distribution (Vd) was also much larger for p-cresol than for creatinine (2.9 +/- 1.4 vs. 0.6 +/- 0.1 L/kg, p<0.01). After injection of p-cresol, an additional chromatographic peak appeared in serum and in urine samples. Although at min 240 serum concentration of p-cresol had decreased to 10% of the peak value, only 23% of the administered amount was excreted in the urine and the CLr was +/- 50% lower compared to that of creatinine. Non-renal clearance and Vd of p-cresol were, however, substantially larger. These data may be of value to explain the different behavior of p-cresol in renal failure and dialysis, compared to creatinine.
引用本文的药物库数据
- 药物