Free Carbamazepine Concentrations and Clinical Outcome

Carbamazepine is effective in the treatment of primary or secondary generalized tonic-clonic epilepsy, all variety of partial seizure, and myoclonic epilepsy. The plasma protein binding of carbamazepine is 70-80%. The primary and active metabolite 10,11-epoxide is only 50% bound to serum proteins. There seems to be less variability in the protein binding of carbamazepine compared with that of phenytoin and valproic acid (67). Froscher et al. (68) showed that in patients with carbamazepine monotherapy, there was no closer relationship between free concentration and pharmacological effects compared with total concentration and pharmacological effects. Lesser et al. (69) found a broad overlapping of unbound carbamazepine causing toxicity and no toxicity. Because 10,11-epoxide has a greater percentage of Fu and is almost equipotent to carba-mazepine, epoxide probably contributes significantly to the pharmacological effects of carbamazepine. Therapeutic monitoring of epoxide along with carbamazepine may be useful especially in patients taking valproic acid or lamotrigine (70,71).

4. when should free anticonvulsant be monitored?

For strongly protein-bound anticonvulsants, such as phenytoin, valproic acid, and carbamazepine, free drug monitoring is strongly recommended in the following cases:

1. Uremic patients

2. Patients with chronic liver disease

3. Patients with hypoalbuminemia (burn patients, elderly, pregnancy, AIDS, etc.)

4. Suspected drug-drug interactions where one strongly protein-bound drug can displace another strongly protein-bound anticonvulsant.

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