Protein Binding of Carbamazepine and Its Epoxide in Maternal and Fetal Plasma at Delivery: Comparison to Other Anticonvulsants

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Abstract
A detailed investigation of the plasma protein binding of carbamazepine (CBZ) and its major metabolite carbamazepine epoxide (CBZE) revealed that both compounds are more extensively bound to plasma proteins in the mother (% free fraction CBZ, 28.4 .+-. 3.0; CBZE, 55.1 .+-. 5.0) than in the fetus (% free fraction CBZ, 31.5 .+-. 2.2; CBZE, 61.5 .+-. 3.1) at the time of birth. Fetal and maternal protein binding is reduced compared to controls (% free fraction CBZ, 26.5 .+-. 2.1; CBZE, 49.1 .+-. 5.7). A correlation of the unbound fraction with various biochemical parameters suggested that among other factors, high bilirubin concentrations in the fetus could be responsible for the relatively increased free fraction of CBZ and CBZE compared to maternal values. As free fraction values of CBZ and CBZE are either the same (CBZ) or slightly higher (CBZE) in women at term compared to nonpregnant controls, a regular monitoring of maternal free fraction values seems unnecessary. For other anticonvulsive drugs like diazepam and valproic acid, monitoring of both total plasma concentrations and free fractions is strongly recommended.

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