In patients with normal renal function, optimal response is often associated with free (unbound) carbamazepine levels above 1.0 mcg/mL, and toxicity may occur when the free carbamazepine is greater than or equal to 4.0 mcg/mL.
Under normal circumstances, the carbamazepine that circulates in blood is 75% protein-bound. Therapies or conditions such as uremia that displace carbamazepine from protein cause a higher free (unbound) fraction of the drug circulating in blood. In uremia, the free carbamazepine level may be a more useful guide for dosage adjustments than the total level. In patients with severe uremia, subtherapeutic total carbamazepine levels in the range of 1.0 to 2.0 mcg/mL may be associated with therapeutic free carbamazepine levels. Toxicity may occur when the free carbamazepine level is greater than or equal to 4.0 mcg/mL (even though the total carbamazepine concentration is <15.0 mcg/mL).
As with the serum levels of other anticonvulsant drugs, total and free carbamazepine levels should be correlated with the patient's clinical condition. They are best used as a guide in dose adjustment.