Lin T H, Sugiyama Y, Sawada Y, Kawasaki S, Iga T, Hanano M
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Drug Metab Dispos. 1988 Mar-Apr;16(2):290-5.
Our previous studies using an in vivo tissue-sampling single-carotid injection method have shown that the transport of DL-propranolol into rat brain is inhibited by the serum from rats with uranyl nitrate-induced acute renal failure. The present studies were designed to examine the effect of serum from patients with renal or liver disease on the transport of DL-propranolol into the rat brain. While the binding of DL-propranolol to serum from cirrhotic patients was significantly decreased compared to normal serum, there was no change for the serum from patients with renal failure. In the carotid injection studies, the brain transport parameters such as the brain uptake index (BUI), the unidirectional extraction ratio (ET), the blood-brain barrier permeability surface area product (PSapp), and PSapp corrected for the unbound fraction (PSuapp) in rats injected with serum from patients with renal failure were significantly reduced to approximately 40-53% of those in controls. No change in BUI, ET, and PSapp was found in rats injected with serum from cirrhotic patients. However, the cirrhotic patients adopted in the present study had relatively mild liver disease (judging from the biochemical blood test), and we cannot refer to the more severe cirrhotic patients only from this study. Moreover, significant correlations were observed between the biochemical parameters (blood urea nitrogen, serum creatinine concentration) representing the degree of renal failure and the transport parameters (ET, PSapp, or PSuapp) of DL-propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前使用体内组织采样单颈动脉注射法进行的研究表明，硝酸铀酰诱导的急性肾衰竭大鼠的血清会抑制DL-普萘洛尔向大鼠脑内的转运。本研究旨在检测肾病或肝病患者的血清对DL-普萘洛尔向大鼠脑内转运的影响。与正常血清相比，DL-普萘洛尔与肝硬化患者血清的结合显著减少，而肾衰竭患者的血清则无变化。在颈动脉注射研究中，给大鼠注射肾衰竭患者的血清后，其脑转运参数，如脑摄取指数（BUI）、单向提取率（ET）、血脑屏障通透表面积乘积（PSapp）以及经未结合分数校正的PSapp（PSuapp），均显著降低至对照组的约40 - 53%。给大鼠注射肝硬化患者的血清后，未发现BUI、ET和PSapp有变化。然而，本研究纳入的肝硬化患者肝病相对较轻（从生化血液检测判断），仅从本研究我们无法推断更严重的肝硬化患者情况。此外，代表肾衰竭程度的生化参数（血尿素氮、血清肌酐浓度）与DL-普萘洛尔的转运参数（ET、PSapp或PSuapp）之间存在显著相关性。（摘要截断于250字）
