Carbamazepine pharmacokinetics

Carbamazepine is absorbed slowly and erratically following oral administration and may vary from generic to generic, resulting in large variations in serum concentrations of the drug. It induces its own drug metabolism and has an active metabolite. It is a substrate for CYP3A4 with minor metabolism by CYP1A2 and CYC2C8. The epoxide metabolite accounts for 25 percent of the dose, is active, and can be inhibited by drugs that inhibit UDP glucuronosyltransferase (UGT), leading to toxicity. Carbamazepine is an inducer of the isozyme families CYP1A2, CYP2C, and CYP3A and UGT enzymes, which may increase the clearance and reduce the efficacy of drugs that they metabolize. It is not as well tolerated by the elderly as are other available antiseizure medications. Carbamazepine induces formation of liver drug-metabolizing enzymes that increase metabolism of the drug itself and may increase the clearance of many other anticonvulsant drugs including clonazepam, lamotrigine, and valproic acid. Carbamazepine metabolism can be inhibited by other drugs (eg, propoxyphene, valproic acid). A related drug, oxcarbazepine, is less likely to be involved in drug interactions.