Nau R, Desel H, Lassek C, Kolenda H, Prange H
Department of Neurology, Georg-August-Universität, Göttingen, Germany.
Clin Pharmacol Ther. 1999 Jul;66(1):25-32. doi: 10.1016/S0009-9236(99)70050-0.
The intravenous administration of tromethamine (INN, trometamol) lowers the intracranial pressure in patients with brain edema. One postulated mechanism of action is the increase of the pH of the cerebrospinal fluid.
To study tromethamine kinetics in serum and cerebrospinal fluid, nine patients with external ventriculostomies and normal serum creatinine values received 60 mmol intravenous tromethamine (Tris 36.34%, pH 11) over 30 minutes. Serum and cerebrospinal fluid were drawn repeatedly, and concentrations were determined by HPLC.
Maximum serum concentrations (Cmax) ranged from 211 to 426 mg/L (median, 302 mg/L). The volume of distribution was 0.34 to 0.86 L/kg body weight (median, 0.53 L/kg), and the elimination half-life in serum (t1/2beta) 3.22 to 8.44 hours (median, 4.53 hours). Cerebrospinal fluid Cmax values ranging from 0.68 to 34.14 mg/L (median, 3.88 mg/L) were observed 1 to 12 hours after the end of the tromethamine infusion (median, 2 hours). AUC(CSF)/AUC(S) as a measure of overall cerebrospinal fluid penetration was 0.015 to 0.46 (median, 0.068). Cerebrospinal fluid Cmax and AUC(CSF)/AUC(S) depended on the function of the blood-cerebrospinal fluid barrier. Cerebrospinal fluid t1/2 (8.52 to 14.2 hours; median, 11.2 hours) was substantially longer than the t1/2beta in serum. In vitro, cerebrospinal fluid concentrations < or =30 mg/L did not influence cerebrospinal fluid pH.
Tromethamine cerebrospinal fluid concentrations will be high enough to increase the pH of the cerebrospinal fluid only at large doses and in patients with a pronounced disruption of the blood-cerebrospinal fluid barrier.
静脉注射氨丁三醇（国际非专利药品名称，缓血酸胺）可降低脑水肿患者的颅内压。一种假定的作用机制是脑脊液pH值升高。
为研究氨丁三醇在血清和脑脊液中的动力学，9例接受外部脑室造瘘术且血清肌酐值正常的患者在30分钟内静脉输注60 mmol氨丁三醇（三羟甲基氨基甲烷36.34%，pH 11）。反复采集血清和脑脊液，并通过高效液相色谱法测定浓度。
血清最大浓度（Cmax）范围为211至426 mg/L（中位数为302 mg/L）。分布容积为0.34至0.86 L/kg体重（中位数为0.53 L/kg），血清消除半衰期（t1/2β）为3.22至8.44小时（中位数为4.53小时）。在氨丁三醇输注结束后1至12小时（中位数为2小时）观察到脑脊液Cmax值范围为0.68至34.14 mg/L（中位数为3.88 mg/L）。作为整体脑脊液渗透指标的AUC(CSF)/AUC(S)为0.015至0.46（中位数为0.068）。脑脊液Cmax和AUC(CSF)/AUC(S)取决于血脑屏障的功能。脑脊液t1/2（8.52至14.2小时；中位数为11.2小时）明显长于血清中的t1/2β。在体外，脑脊液浓度≤30 mg/L不会影响脑脊液pH值。
仅在大剂量以及血脑屏障明显破坏的患者中，氨丁三醇的脑脊液浓度才会高到足以升高脑脊液pH值。
