<i>OPRD1</i> rs569356 polymorphism has an effect on plasma norbuprenorphine levels and dose/kg-normalized norbuprenorphine values in individuals with opioid use disorder

AKYÜZLÜ D., Ozkan-Kotiloglu S., Danisman M., BAL C., Ogur B., Ispir G. Z.

ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, cilt.100, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 100
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.etap.2023.104143
  • Dergi Adı: ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Greenfile, MEDLINE, Pollution Abstracts, Veterinary Science Database
  • Ankara Üniversitesi Adresli: Evet

Özet

This study aimed to determine the effects of nine OPRM1, OPRD1 and OPRK1 polymorphisms on plasma BUP and norbuprenorphine (norBUP) concentrations and various treatment responses in a sample of 122 patients receiving BUP/naloxone. Plasma concentrations of BUP and norBUP were detected by LC-MS/MS. PCR-RFLP method was used to genotype polymorphisms. OPRD1 rs569356 GG had significantly lower plasma norBUP concentration (p = 0.018), dose-(p = 0.049) and dose/kg-normalized norBUP values (p = 0.036) compared with AA. Craving and withdrawal symptoms were significantly higher in OPRD1 rs569356 AG+GG relative to AA. There was a statistically significant difference between the OPRD1 rs678849 genotypes in the intensity of anxiety (13.5 for CT+TT and 7.5 for TT). OPRM1 rs648893 TT (18.8 +/- 10.8) was significantly different to CC+CT (14.82 +/- 11.3; p = 0.049) in view of the intensity of depression. This current study provides the first data on a prominent effect of the OPRD1 rs569356 variation on BUP pharmacology due to its metabolite norBUP.