Kinetics and metabolism of carbamazepine during combined antiepileptic drug therapy.
The kinetics of carbamazepine using 15N-carbamazepine were investigated in epileptic patients during combined anticonvulsant therapy. The 15N-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, phenobarbital, ethosuximide, or methsuximide further induces carbamazepine metabolism.
D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male
D000927:Anticonvulsants; D002220:Carbamazepine