Entry of tromethamine into the cerebrospinal fluid of humans after cerebrovascular events

Objective: The intravenous administration of tromethamine (INN, trometamol) lowers the intracranial pressure in patients with brain edema. One postula ted mechanism of action is the increase of the pH of the cerebrospinal flui d. Methods: To study tromethamine kinetics in serum and cerebrospinal fluid, n ine patients with external ventriculostomies and normal serum creatinine va lues received 60 mmol intravenous tromethamine (Tris 36.34%, pH 11) over 30 minutes. Serum and cerebrospinal fluid were drawn repeatedly, and concentr ations were determined by HPLC. Results: Maximum serum concentrations (C-max) ranged from 211 to 426 mg/L ( median, 302 mg/L). The volume of distribution was 0.34 to 0.86 L/kg body we ight (median, 0.53 L/kg), and the elimination half-life in serum (t(1/2)bet a) 3.22 to 8.44 hours (median, 4.53 hours). Cerebrospinal fluid C-max value s 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(CS F)/AUC(S) as a measure of overall cerebrospinal fluid penetration was 0.015 to 0.46 (median, 0.068). Cerebrospinal fluid C-max and AUC(CSF)/AUC(S) dep ended on the function of the blood-cerebrospinal fluid barrier. Cerebrospin al fluid t(1/2) (8.52 to 14.2 hours; median, 11.2 hours) was substantially longer than the t(1/2)beta in serum. In vitro, cerebrospinal fluid concentr ations less than or equal to 30 mg/L did not influence cerebrospinal fluid pH. Conclusion: Tromethamine cerebrospinal fluid concentrations will be high en ough to increase the pH of the cerebrospinal fluid only at large doses and in patients with a pronounced disruption of the blood-cerebrospinal fluid b arrier.