Pharmacogenetics of nevirapine excretion into breast milk and infants’ exposure through breast milk versus postexposure prophylaxis

Abstract

Aim: The influence of genetic factors on nevirapine (NVP) breast milk pharmacokinetics and breastfed infants’ exposure were investigated. Patients & methods: Associations between nine SNPs in NVP disposition genes in mothers and its plasma and breast milk concentrations were explored in nursing mother–infant pairs. Results: NVP pharmacokinetics in maternal plasma, breast milk and infant exposure indices were influenced by CYP2B6 516G>T and 983T>C. The median (range) milk-to-plasma area under the curve (AUC0–12) ratio was 0.95 (0.56–1.5). Calculated as percentages of pediatric treatment, infant postexposure prophylaxis and maternal weight-adjusted doses, the maximum exposure indices were 3.64% (1.99–9.88), 26.0% (9.93–79.1) and 13.8% (5.77–27.7), respectively. Infant plasma concentration as a result of exposure through breast milk (n = 93), pre-exposure prophylaxis (n = 10) and both (n = 27) were 660 (104–3090), 1020 (401–3325) and 2720 ng/ml (1360–7290), respectively. Conclusion: The clinical significance of the observed differences between routes of infants’ exposure warrants further investigation.