RESUMO
OBJECTIVES: Understanding the influence of fetal and maternal genetics on prenatal drug exposure could potentially improve benefit-risk evaluation. In this study, we investigated the impact of two functional polymorphisms in CYP2B6 on prenatal exposure to efavirenz. METHODS: Dried blood spot (DBS) samples were collected from HIV-positive pregnant women (nâ =â 112) and their newborns (nâ =â 107) at delivery. They were genotyped for single nucleotide polymorphisms in CYP2B6. Efavirenz was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Significant correlations were observed in efavirenz concentration between maternal and newborn (râ =â 0.46, R2â =â 0.21, Pâ <â 0.001), and maternal and cord (râ =â 0.83, R2â =â 0.68, Pâ <â 0.001) samples. Median (interquartile range) newborn plasma-to-maternal plasma and cord-to-maternal plasma ratios were 0.85 (0.03-3.49) and 0.78 (0.23-1.96), respectively. Newborn efavirenz concentration in DBS varied significantly based on composite maternal CYP2B6 genotype: fast (CYP2B6 516GG and 983TT, nâ =â 26), 747â ng/ml (602-1060); intermediate (CYP2B6 516GT or 983TC nâ =â 50), 1177 ng/ml (898-1765); and slow (CYP2B6 516GT and 983TC or 516TT or 983CC, nâ =â 14), 3094 ng/ml (2126-3812). Composite newborn CYP2B6 genotype was, however, not significantly associated with prenatal exposure. Efavirenz concentration in newborn stratified as fast (nâ =â 25), intermediate (nâ =â 36), and slow metabolizers (nâ =â 19) from prenatal exposure was 999.7â (774-1285), 1240 (709-1984), and 1792 ng/ml (1201-3188), respectively. CONCLUSION: The clinical relevance of the observed influence of maternal genetics on prenatal efavirenz exposure requires further investigation.