Oxcarbazepine.
The success of carbamazepine (CBZ) as a broad-spectrum antiepileptic drug (AED) has led to its use as first-line therapy in children and adults for partial and generalized tonic-clonic seizures. The limitations of CBZ include toxicity in sensitive individuals, autoinduction, which requires dose adjustment when therapy is initiated, and chronic hepatic induction, producing drug interactions when CBZ is used with AEDs and other drugs that undergo hepatic metabolism. One of two main products of CBZ microsomal metabolism, CBZ-10,11-epoxide (formed by oxidation of the double bond between C-10 and C-11), appears to provide antiepileptic efficacy but contributes significantly to clinical toxicity. The most common adverse effects of CBZ are central nervous system (CNS) symptoms, followed by gastrointestinal, hepatic, endocrine disturbances, and teratogenic effects. Oxcarbazepine (OXC) was developed to provide a compound chemically similar enough to CBZ to mimic its efficacy and overall safety while improving its side-effect profile. Biotransformation of OXC does not involve formation of an epoxide metabolite. Compared with the parent compound, hepatic microsomal enzyme induction and autoinduction are greatly reduced. The clinical efficacy of OXC compares favorably with CBZ in clinical trials. Clinical development of OXC began in Europe. Results of Phase I trials started to appear in the early 1980s. Controlled clinical trials, reported in the mid- to late 1980s, led to approval of OXC in many European countries, and now in over 50 nations around the world. United States multicenter clinical trials have recently been completed, and at this writing the drug is awaiting approval by the FDA. This article reviews the pharmacology, animal data, outcomes of published controlled clinical trials, postmarketing data, adverse experiences, and current recommendations for clinical use of OXC.
Tecoma
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UCSD Epilepsy Center, University of California, San Diego 92037, USA.
D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001682:Biological Availability; D001711:Biotransformation; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D018849:Controlled Clinical Trials as Topic; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D000078330:Oxcarbazepine; D010672:Phenytoin / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000927:Anticonvulsants; D002220:Carbamazepine; D010672:Phenytoin; D000078330:Oxcarbazepine