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 postulated mechanism of action is the increase of the pH of the cerebrospinal fluid.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Nau
R
R
Department of Neurology, Georg-August-Universität, Göttingen, Germany. rnau@gwdg.de
Desel
H
H
Lassek
C
C
Kolenda
H
H
Prange
H
H
D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000134:cerebrospinal fluid* / Q000150:complications / Q000503:physiopathology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007427:Intracranial Pressure / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D014325:Tromethamine / Q000378:metabolism* / Q000627:therapeutic use
D014325:Tromethamine