蛋白结合的动力学,亲脂性的,尿毒症毒素p-cresol健康老鼠。

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Lesaffer G迪斯美特R D 'heuvaert T, Belpairea调频,Lameire N, Vanholder R

蛋白结合的动力学,亲脂性的,尿毒症毒素p-cresol健康老鼠。

生命科学。2001年9月28日,69 (19):2237 - 48。

PubMed ID

11669466 (在PubMed

]

文摘

P-Cresol,部分亲脂性的,蛋白结合的化合物与几个生化改变尿毒症。因为p-cresol动力学从未被研究过,我们在大鼠研究其动力学行为。结果与同肌酸酐相比,水溶性,non-protein-bound尿毒症保留溶质,目前用作尿毒症保留的标志。健康的老鼠分成三个小组,可比体重:(1)对照组(n = 6);(2)一组(n = 7)收到了一封静脉3毫克p-cresol丸;和(3)一组(n = 5)收到18毫克肌酐的静脉团。收集血液样本在0、5、30、60、120、180和240分钟后政府的决心p-cresol和肌酐。每隔小时尿液收集。高效液相色谱p-Cresol浓度进行了评估。p-cresol和肌酐的药代动力学参数计算使用non-compartmental从血清浓度时间曲线分析。 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.

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