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Kinetics and metabolism of carbamazepine during combined antiepileptic drug therapy
Author(s) -
Eichelbaum M.,
Köthe K. W.,
Hoffmann F.,
Unruh G. E.
Publication year - 1979
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 - 10.1002/cpt1979263366
Subject(s) - carbamazepine , antiepileptic drug , drug metabolism , pharmacology , anticonvulsant , drug , medicine , epilepsy , psychiatry
The kinetics of carbamazepine using 15 N‐carbamazepine were investigated in epileptic patients during combined anticonvulsant therapy. The 15 N‐carbamazepine plasma half‐lives ranged from 5.0 to 13.6 hr with a mean of 8.2 hr. These half‐lives are appreciably shorter than reported during chronic carbamazepine monotherapy. Predicted steady‐state plasma levels and observed plasma levels of carbamazepine were in excellent agreement. Between 32% and 61% of the dose administered is excreted in the urine as carbamazepine‐trans‐diol, 5.2% to 8.8% as 9‐hydroxymethyl‐10‐carbamoyl acridane, 1% to 1.4% as 10,‐11‐carbamazepine epoxide, and 0.5% as carbamazepine. The data indicate that it is the epoxide‐diol pathway which is induced during long‐term treatment. Concomitant therapy with primidone, phenytoin, phénobarbital, ethosuximide, or methsuximide further induces carbamazepine metabolism.