Monitoring carbamazepine (free) therapy in uremic patients
Monitoring unbound or free carbamazepine levels in patients where the total carbamazepine result is within the therapeutic range but the patient is experiencing side effects.
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.