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

Medicine (Baltimore). 2018 Jul;97(30):e11662. doi: 10.1097/MD.0000000000011662.

Abstract

Carbamazepine (CBZ) is a widely used antiepileptic drug with large interindividual variability in serum concentrations. Previous studies found that CYP3A5*3 (rs776746), UGT2B7*2 (802C>T), and UGT2B7*3 (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 CYP3A5*3, UGT2B7*2, and UGT2B7*3. 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 CYP3A5*3 and UGT2B7*3 patients (all P < .05), but not in UGT2B7*2 patients (P = .1080). UGT2B7*2 patients exhibited lower dose-normalized CBZ concentrations and larger CBZ dose requirements than UGT2B7*1/*1 patients (P = .0139, P = .032, respectively). There were no differences between UGT2B7*3, UGT2B7*1/*1 and CYP3A5*3, and CYP3A5*1/*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 UGT2B7*2 variant, but not the CYP3A5*3 or UGT2B7*3 variant, could affect steady-state CBZ concentrations in epileptic patients.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / blood*
  • Asian People / genetics*
  • Body Weight
  • Carbamazepine / administration & dosage
  • Carbamazepine / blood*
  • Cytochrome P-450 CYP3A / genetics*
  • Epilepsy / blood
  • Epilepsy / drug therapy*
  • Epilepsy / genetics*
  • Female
  • Genotype
  • Glucuronosyltransferase / genetics*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Young Adult

Substances

  • Anticonvulsants
  • Carbamazepine
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • UGT2B7 protein, human
  • Glucuronosyltransferase