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Acute Hepatotoxicity After Excessively High Doses of Carbamazepine on Two Occasions
Author(s) -
Luke David R.,
Rocci Mario L.,
Schaible Deborah H.,
Ferguson Roger K.
Publication year - 1986
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1986.tb03463.x
Subject(s) - lethargy , carbamazepine , metabolite , anticonvulsant , medicine , anesthesia , central nervous system , convulsion , pharmacology , chemistry , epilepsy , psychiatry
A 2½‐year‐old child being treated with carbamazepine (CBZ) for a seizure disorder on two separate occasions experienced elevated CBZ serum concentrations (28 and 23.2 mg/L), severe liver damage (SGOT > 6000 IU, SGPT > 5000 IU), and central nervous system manifestations (coma, lethargy, seizures). During the first episode, the time course of CBZ concentrations exhibited a nonlinear decline and was accompanied by CBZ‐10,11‐epoxide concentrations that were elvated 4‐fold compared to normal values. Cerebrospinal fluid concentrations of CBZ and CBZ‐10,11‐epoxide were also elevated, although their ratios to serum concentrations did not suggest enhanced permeability of the central nervous system to these substances. The concentrations of CBZ‐10,11‐epoxide but not CBZ were elevated for the duration of time that the patient was comatose, suggesting that this metabolite may contribute to the neurotoxic side effects observed with CBZ therapy.