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Entry of tromethamine into the cerebrospinal fluid of humans after cerebrovascular events
Author(s) -
Nau Roland,
Desel Herbert,
Lassek Christoph,
Kolenda Herbert,
Prange Hilmar
Publication year - 1999
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(99)70050-0
Subject(s) - cerebrospinal fluid , cmax , medicine , anesthesia , chemistry , pharmacokinetics
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 (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 weight (median, 0.53 L/kg), and the elimination half‐life in serum (t ½ β) 3.22 to 8.44 hours (median, 4.53 hours). Cerebrospinal fluid C max 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 C max and AUC CSF /AUC S depended on the function of the blood–cerebrospinal fluid barrier. Cerebrospinal fluid t ½ (8.52 to 14.2 hours; median, 11.2 hours) was substantially longer than the t ½ β in serum. In vitro, cerebrospinal fluid concentrations ≤30 mg/L did not influence cerebrospinal fluid pH. Conclusion 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. Clinical Pharmacology & Therapeutics (1999) 66 , 25–32;