Pharmacogenetic exploration of buprenorphine and related metabolites in umbilical cord blood

Abstract

The goal of this study was to explore associations between single-nucleotide polymorphisms (SNPs) and umbilical cord blood concentrations of buprenorphine and its metabolites following maternal administration. This is a sub-study of a prospective observational cohort investigation which included pregnant women receiving buprenorphine for opioid use disorder during pregnancy. Following delivery, umbilical cord blood samples were collected and genotyped using a pharmacogenetic panel. The drug and metabolite concentrations were analyzed through liquid chromatography-mass spectrometry, and genetic association analysis was completed using PLINK software. The included neonates (n = 14) had a mean birth weight of 3.00 ± 0.39 kg and were born to mothers receiving a mean buprenorphine dose of 10.29 ± 6.22 mg. Ten concentration groupings (drug, single metabolite, as well as drug/metabolite(s) combinations) produced 18 unique SNP associations. Two significant associations included variations in CYP3A4 and UGT1A1, which play a role in the metabolism of buprenorphine. These preliminary findings suggest potential pharmacogenetic factors influencing fetal drug exposure, warranting larger studies to validate associations and explore clinical implications for neonatal outcomes.