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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:97 |
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| Enthalten in: |
Medicine - 97(2018), 30 vom: 01. Juli, Seite e11662 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lu, Qiong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.08.2018 Date Revised 07.12.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/MD.0000000000011662 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM286854902 |
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| 245 | 1 | 0 | |a Effects of CYP3A5 and UGT2B7 variants on steady-state carbamazepine concentrations in Chinese epileptic patients |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Qu, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Jian |e verfasserin |4 aut | |
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