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目的 了解多奈哌齐透过小鼠血脑屏障的转运机制。方法 采用反相高效液相色谱法及Integrationplot法定量解析 ,以多奈哌齐在脑内浓度 (cb)对血浆中浓度 (cp)比值 (Kp)为纵轴 ,血浆中浓度曲线下面积对血浆中浓度比 (AUC/cp)为横轴 ,通过计算机模拟软件进行Integrationplot并求出药物流入脑内的速度常数 (K1)及排出速度常数 (K2 )的比值 ,以此定量反映药物移行入脑的过程。结果 Integrationplot所得结果为抛物线 ,K1(mL·s-1g-1) =0 .0 0 12 1± 0 .0 0 0 16 ,K2 (s-1) =0 .0 0 2 2 7± 0 .0 0 0 37,K1/K2 =0 .5 4 1,当AUC/cP 值在 2 0 0 0s左右时 ,KP 值达到稳定状态。显示多奈哌齐在初期向脑内快速转运 ,后期多奈哌齐的脑内转运和泵出逐渐达到平衡状态。结论 脑内存在着运载多奈哌齐排出脑组织的载体
Objective To understand the transport mechanism of donepezil through the blood-brain barrier in mice. Methods The RP-HPLC and Integrationplot method were used for quantitative analysis. Donepezil in the brain concentration (cb) to plasma concentration (cp) ratio (Kp) as the vertical axis, the plasma concentration under the curve of the plasma concentration ratio (AUC / cp) on the horizontal axis, and the Integrationplot was calculated by computer simulation software to determine the ratio of the velocity constant (K1) and the discharge velocity constant (K2) of the drug flowing into the brain, thereby quantitatively reflecting the migration of the drug into the brain. Results The result of Integrationplot was a parabola. K1 (mL · s-1g-1) = 0.012 1 ± 0.00016, K2 (s-1) = 0.00227 ± 0 .0 0 0 37, K1 / K2 = 0 .5 4 1. When the AUC / cP value is around 2 0 0s, the KP value reaches a steady state. It was shown that donepezil rapidly translocated to the brain in the early stage, and the posttransplant and pump out of donepezil gradually reached the equilibrium state. Conclusion There is a carrier in the brain that carries donepezil to expel brain tissue