Nakazono T, Murakami T, Sakai S, Higashi Y, Yata N
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Chem Pharm Bull (Tokyo). 1992 Sep;40(9):2510-5. doi: 10.1248/cpb.40.2510.
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 biological 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 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 in vivo experiments. Calculated curves were well fitted on observed caffeine concentrations in the plasma, brain and CSF.
在大鼠静脉注射咖啡因后，研究了微透析法用于按时间顺序测定大脑和脑脊液（CSF）中咖啡因浓度的实用性。测定了微透析法对咖啡因的回收率，即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。结果证明，在5种不同的咖啡因稳态血浆浓度（0.1 - 280 nmol/ml）以及不同的透析液收集时间段（从30秒到10分钟）内，回收率保持恒定。大脑和脑脊液中的平均回收率分别为10.9%和13.1%。因此，微透析法被证明可用于测定组织和生物体液中的药物浓度，时间分辨率超过30秒。随后，微透析法被应用于静脉推注给药后按时间顺序测定大脑和脑脊液中的咖啡因浓度。估计的大脑和脑脊液中的咖啡因浓度分别与通过直接测定分离的大脑和脑脊液所获得的浓度相同。使用改进的二室模型进一步对咖啡因从血浆向大脑和脑脊液的转运进行了药代动力学分析。在这个动力学模型中，由于在体内实验中未检测到咖啡因在脑脊液和大脑之间的相互转运，因此忽略了咖啡因在脑脊液和大脑之间的转运。计算曲线与观察到的血浆、大脑和脑脊液中的咖啡因浓度拟合良好。
