Study on Drug Distribution into Brain and Cerebrospinal Fluid by Microdialysis

微透析的有用性进行了检查，按时间顺序测定咖啡因在大鼠脑和脑脊液（CSF）中的浓度静脉注射咖啡因后。测定了微透析咖啡因的回收率、透析液中咖啡因浓度与脑组织或脑脊液中咖啡因浓度的比值。在5种不同的咖啡因稳态血浆浓度（0.1 - 280 nmol/ml）和不同的透析液收集时间（30 s-10 min）下，回收率是恒定的，脑和脑脊液中的平均回收率分别为10.9%和13.1%。因此，微透析被证明是有用的，用于测定药物浓度的组织和生物液体的时间分辨率超过30秒。然后应用微透析方法按时间顺序测定咖啡因浓度在脑和CSF静脉推注给药后。脑和脑脊液中咖啡因浓度的估计值分别与直接测定离体脑和脑脊液中咖啡因浓度的结果相同。使用改良的二室模型进一步分析咖啡因从血浆向脑和CSF的转移。在该动力学模型中，咖啡因在CSF和脑之间的转移被忽略，因为在体内实验中没有检测到咖啡因的相互转移。计算的曲线与血浆、脑和CSF中观察到的咖啡因浓度拟合良好。

The usefulness of microdialysis was examined for the chronological determination of caffeine concentration in the brain and cerebrospinal fluids (CSF) following intravenous administration of caffeine in rats. The recovery percent of caffeine by microdialysis, the concentration ratio of caffeine in the dialysate against that in the brain tissue or CSF was determined. The recovery percent was proved to be constant at 5 different steady -state plasma concentrations of caffeine (0.1 - 280 nmol/ml) and in different collecting periods of dialysate ranging from 30 s to 10 min. The mean recovery percent in the brain and CSF were 10.9 and 13.1%, respectively. Thus, microdialysis was proved useful for determination of drug concentration in the tissue and bilogical fluids with time resolution of more than 30 s.The microdialysis method was then applied for the chronological determination of caffeine concentration in the brain and CSF following intravenous bolus administration. The estimated caffeine concentration in the brain and CSF was as the same as those obtained by direct determination in isolated brain and CSF, respectively. Transfer of caffeine from plasma to brain and CSF were further pharmacokinetically analyzed using a modified 2-compartment model. In this kinetic model, the transfer of caffeine between the CSF and brain was neglected, since the mutual transfer of caffeine was not detected in vivo experiments. Calculated curves were well fitted on observed caffeine concentrations in the plasma, brain and CSF.