Pharmacogenetics of nevirapine excretion into breast milk and infants' exposure through breast milk versus postexposure prophylaxis.
The influence of genetic factors on nevirapine (NVP) breast milk pharmacokinetics and breastfed infants' exposure were investigated.



Associations between nine SNPs in NVP disposition genes in mothers and its plasma and breast milk concentrations were explored in nursing mother-infant pairs.



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.



The clinical significance of the observed differences between routes of infants' exposure warrants further investigation.
Department of Molecular & Clinical Pharmacology, University of Liverpool, 70 Pembroke Place, Liverpool L69 3GF, UK.|Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
Adeniyi
A
Olagunju
Department of Molecular & Clinical Pharmacology, University of Liverpool, 70 Pembroke Place, Liverpool L69 3GF, UK.
Saye
S
Khoo
Department of Molecular & Clinical Pharmacology, University of Liverpool, 70 Pembroke Place, Liverpool L69 3GF, UK.
Andrew
A
Owen
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D008895:Milk, Human / Q000378:metabolism*; D019829:Nevirapine / Q000493:pharmacokinetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D056990:Post-Exposure Prophylaxis
D019380:Anti-HIV Agents; D019829:Nevirapine
CYP2B6; breast milk; infant exposure; nevirapine; pharmacokinetics