咖啡因在大白鼠之藥物動力學及在腦部之分佈

Pharmacokinetics and Brain Regional Distribution of caffeine in Rats

為了探討咖啡因在大白鼠之藥物動力學及在腦部之分佈，本研究首先建立了一套對含咖啡因血液及腦組織檢品前處理及液相層析之快速分析方法。血漿及腦組織均質液檢品都以氧甲烷處理，使蛋白質沉澱，然後再離心以分開蛋白質。離心後的上清液以碳-18 之逆相層析分離管柱，配合移動相溶液 0.1M 硼酸緩衝溶液(pH6.4)－－甲醇(72: 28，v/v)，進行定量分析。本研究方法分析咖啡因的偵測極限是0.01ug/ml。動物實驗結果顯示，大白鼠靜脈注射咖啡因 2mg/kg 後，在血液呈現符合二室休之藥物動力學模式，其體內血液的排除半衰期是77.2 土 4.4 分鐘。在大白鼠靜脈注射咖啡因後 15 分鐘，將大白鼠犧牲，進一步分析大白鼠腦部各組織中的咖啡因濃度，包括大腦皮質、小腦、海馬迴、幹腦、紋狀體及中腦，結果發現咖啡因在大白鼠腦部各組織中的濃度沒有顯著差異。

A liquid chromatographic method with a rapid clean-up procedure was used for the determination of caffeine in rat plasma and brain tissue after administration of a single dose of caffeine (2 mg/kg, iv). Plasma and brain tissue homogenates were deproteinated by acetonitrile and then centrifuged. Separa- tion was achieved on a Cosmosile C18 column with a mobile phase of 0.1 M borate buffer (pH 6.4)- methanol (72:28, v/v). The limit of detection of caffeine was 0.01 ug/mL. The results suggest that the plasma concentration versus time profile of caffeine fits a two-compartment open model, and that the elimination half-life of caffeine is 77.2 ± 4.4 min in rat blood. Fifteen min after caffeine administration, there were no significant differences in caffeine concentration among various regions of the rat brain (cerebral cortex, cerebellum, hippocampus, brain stem, striatum and midbrain).