The effects of<i> UGT1A4</i> and<i> ABCB1</i> polymorphisms on clozapine and Ndesmethyl clozapine plasma levels in Turkish schizophrenia patients

Ozdemir F., Oz M. D., Tok K. C., Dural E., Kır Y., Gumustas M., ...Daha Fazla

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.taap.2024.117219
  • Dergi Adı: TOXICOLOGY AND APPLIED PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Environment Index, Veterinary Science Database
  • Anahtar Kelimeler: ABCB1, Clozapine, Schizophrenia, Turkish, UGT1A4
  • Ankara Üniversitesi Adresli: Evet

Özet

Clozapine (CLZ) is an antipsychotic which is particularly used in treatment resistant schizophrenia patients who do not respond to other agents. It is preferred because it reduces suicidal behaviours and attempts, reducing aggression and violent behaviour. The aim of the study is to evaluate the effects of ABCB1 rs1045642 and UGT1A4 rs2011425 polymorphisms on CLZ and its major metabolite Ndesmethly clozapine (DCLZ) plasma concentrations in patients with schizophrenia. A total 109 of Turkish patients with schizophrenia on continually administered CLZ monotherapy were included. The plasma concentrations of CLZ and DCLZ were measured using an HPLC after liquid-liquid extraction while, transporter gene ABCB1 and phase two enzyme UGT1A4 polymorphisms were identified using PCR- RFLP method. Results showed that UGT1A4*3 polymorphism has statistically significant effects on CLZ C/D and DCLZ C/D levels in patients with sub/supra therapeutic levels while ABCB1 C3435T polymorphism has a significant effect on CLZ/DCLZ ratio among patients who have subtherapeutic levels. This study indicates the influence of genetic differences on plasma levels and highlights the importance of pharmacogenetic studies in clinic. Using the obtained results as pharmacogenetic biomarkers will help clinicians provide effective treatment in individual patients and reduce the undesirable side effects.