Clinical Information

Carbamazepine (Tegretol) is an effective treatment for complex partial seizures, with or without generalization to tonic-clonic seizures.(1) It is frequently administered in conjunction with other antiepileptic agents, such as phenytoin and valproic acid.(2) Under normal circumstances, the carbamazepine that circulates in blood is 70% to 80% protein-bound;(3) only the free drug is able to enter the interstitial space in the brain where the pharmacological effects occur.(4)

Patient management is best guided by monitoring free serum concentrations when protein binding is altered. Altered protein binding occurs in patients with hypoalbuminemia observed during pregnancy, in the malnourished, and liver disease. In patients with kidney disease, uremia may develop whose byproducts can displace bound carbamazepine increasing the unbound fraction. Administration of drugs that can compete for serum protein binding sites may also increase the unbound fraction of carbamazepine. Since neurologic activity and toxicity of carbamazepine are directly related to the circulating free fraction of drug, adjustment of dosage based on knowledge of the free carbamazepine concentration may be more useful in these patient populations.