Carbamazepine and its major metabolites in plasma: a summary of eight years of therapeutic drug monitoring

For a period of 8 years, carbamazepine (CBZ) and its two major metabolites carbamazepine-10,11-epoxide (CBZE) and 10,11-dihydroxy-carbamazepine (CBZH) were monitored in plasma of black and white patients visiting outpatient epilepsy clinics. Mean CBZ, CBZE, and CBZH levels found in the black group (n = 451) were found to be significantly lower (p less than 0.0005) than in white patients (n = 2,225). The ratio of CBZE to CBZ levels was found to be significantly lower (p less than 0.0005) for blacks, with CBZ levels within the therapeutic range (5-10 micrograms/ml); the ratio of CBZH to CBZ levels was higher (p less than 0.0005), while there was no significant difference in the ratio of CBZH to CBZE between the two groups. This may indicate a difference in the monooxygenase enzyme activities, whereas the epoxide hydrase activity is probably the same for both groups. A poor linear correlation exists between CBZH and CBZ levels in both groups (for blacks, r = 0.614, n = 451; for whites, r = 0.338, n = 2,225); the correlation is better between CBZE and CBZ (for blacks, r = 0.745; for whites, r = 0.553) and good between CBZH and CBZE (for blacks, r = 0.752; for whites, r = 0.710). Abnormal ratios of CBZH to CBZE were found to be useful indicators of noncompliance in difficult cases presenting with therapeutic levels of CBZ.