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Lorazepam conjugation is unimpaired in burn trauma
Author(s) -
Martyn Jeevendra,
Greenblatt David J
Publication year - 1988
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 - 10.1038/clpt.1988.29
Subject(s) - lorazepam , diazepam , burn injury , intravenous bolus , medicine , glucuronidation , volume of distribution , anesthesia , bolus (digestion) , clinical pharmacology , gastroenterology , pharmacology , pharmacokinetics , surgery , chemistry , biochemistry , enzyme , microsome
A previous clinical study documented impaired hepatic metabolism of diazepam (phase I reaction) after burn injury. In this study, using lorazepam as a marker of hepatic glucuronidation, we tested the hypothesis that after burn injury, phase II reactions may be less impaired than phase I reactions. Ten burned patients and 10 age‐, weight‐, and sex‐matched control subjects were studied after a 2 mg bolus dose of lorazepam. Burned patients had received multiple medications, whereas control patients were not taking any medication. The burned patients were studied at a mean (± SE) of 22 (± 4.6) days after burn injury. The burned patients had increases in total volume of distribution (2.66 ± 0.55 vs. 1.39 ± 0.1L/kg; P < 0.02) and clearance (4.28 ± 1.20 vs. 1.16 ± 0.1 ml/min/kg; P < 0.01), whereas the half‐life was significantly reduced in the burned group (9.6 ± 1.3 vs. 13.9 ± 0.9 hours; P < 0.025). The significantly increased clearance and decreased elimination half‐life in burned patients indicates that the elimination kinetics of lorazepam are not impaired and in fact may be enhanced in burned patients. Clinical Pharmacology and Therapeutics (1988) 43, 250–255; doi: 10.1038/clpt.1988.29