Iwamoto K, Watanabe J, Satoh M
Biochem Pharmacol. 1986 Aug 15;35(16):2677-81. doi: 10.1016/0006-2952(86)90174-7.
Overall initial uptake rates of propranolol by isolated rat hepatocytes were analyzed to give both apparently linear and saturable processes. The rate constant for the linear transport process in 7- and 24-week old rats was approximately 0.01 ml X sec-1 X (10(6) cells)-1. For the capacity-limited uptake process of propranolol, the kinetic parameters in 7-week-old rats, were estimated as Vmax = 0.609 microgram X (10(6) cells)-1 X sec-1 and Km = 8.17 micrograms/ml, whereas in 24-week-old rats, Vmax = 0.348 microgram X (10(6) cells)-1 X sec-1 and Km = 9.40 micrograms/ml. The overall uptake rate, when the hepatocytes were incubated with 20 micrograms/ml of propranolol, was reduced with age of the rats between 5 or 7 and 24 weeks and declined gradually thereafter, A higher cell to medium concentration ratio for the initially, net transported component of propranolol in relatively young (5- to 11-week-old) rats suggested an age-dependent saturable uptake process. This was supported by the direct comparison of the saturable uptake rates between 7 and 24 weeks. Therefore, the saturable sinusoidal transport (i.e. saturable uptake by the hepatocytes) may be considered one of the most important mechanisms determining the age-dependence in the intrinsic hepatic clearance of this drug noted in our previous report.
分析了分离的大鼠肝细胞对普萘洛尔的总体初始摄取率，以给出明显的线性和饱和过程。7周龄和24周龄大鼠线性转运过程的速率常数约为0.01 ml×sec-1×(10⁶细胞)-¹。对于普萘洛尔的容量限制摄取过程，7周龄大鼠的动力学参数估计为Vmax = 0.609微克×(10⁶细胞)-¹×sec-¹，Km = 8.17微克/毫升，而在24周龄大鼠中，Vmax = 0.348微克×(10⁶细胞)-¹×sec-¹，Km = 9.40微克/毫升。当肝细胞与20微克/毫升普萘洛尔孵育时，总体摄取率在5或7周龄至24周龄的大鼠中随年龄降低，此后逐渐下降。相对年轻（5至11周龄）大鼠中普萘洛尔初始净转运成分的细胞与培养基浓度比更高，表明存在年龄依赖性饱和摄取过程。7周龄和24周龄之间饱和摄取率的直接比较支持了这一点。因此，饱和的肝血窦转运（即肝细胞的饱和摄取）可能被认为是决定我们先前报告中该药物肝脏内在清除率年龄依赖性的最重要机制之一。
