Effects of CYP3A5 and UGT2B7 variants on steady-state carbamazepine concentrations in Chinese epileptic patients.

Carbamazepine (CBZ) is a widely used antiepileptic drug with large interindividual variability in serum concentrations. Previous studies found that CYP3A53 (rs776746), UGT2B72 (802C>T), and UGT2B73 (211G>T) variants could change the enzymes' activity, which may influence drug concentrations. Our study aims to investigate whether these variants affect steady-state CBZ concentrations in Chinese epileptic patients. In our study, 62 epileptic patients who received CBZ as monotherapy were monitored for steady-state CBZ concentrations. We used polymerase chain reaction (PCR)-based Sanger sequencing to assess the variants CYP3A53, UGT2B72, and UGT2B73. The results showed a positive correlation between dose and CBZ serum concentration in all patients and in patients with 3 different variants (all P < .05). After CBZ concentrations were normalized by the dose administered, negative correlations between dose-normalized CBZ concentrations and CBZ doses were observed in all patients, and in CYP3A53 and UGT2B73 patients (all P < .05), but not in UGT2B72 patients (P = .1080). UGT2B72 patients exhibited lower dose-normalized CBZ concentrations and larger CBZ dose requirements than UGT2B71/1 patients (P = .0139, P = .032, respectively). There were no differences between UGT2B73, UGT2B71/1 and CYP3A53, and CYP3A51/*1 patients with regard to steady-state CBZ concentration, dose-normalized concentration, required CBZ dose, and body weight-normalized dose (all P > .05). Moreover, a significant difference in body weight-normalized CBZ dose between UGT2B7 GC and TT haplotype patients was observed (P = .0154). In conclusion, our study found that the UGT2B72 variant, but not the CYP3A53 or UGT2B73 variant, could affect steady-state CBZ concentrations in epileptic patients.