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 (AUC_0–12) 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.

Keywords::

• breast milk
• CYP2B6
• infant exposure
• nevirapine
• pharmacokinetics

Acknowledgements

The authors would like to thank the participating patients and staff at collaborating clinical sites in Benue State, Nigeria for their support.

Financial & competing interests disclosure

This work was supported by a grant from Tertiary Education Trust Fund of Nigeria for A Olagunju's PhD at the University of Liverpool, UK. The sponsor had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by a grant from Tertiary Education Trust Fund of Nigeria for A Olagunju's PhD at the University of Liverpool, UK. The sponsor had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.