Breast milk pharmacokinetics of efavirenz and breastfed infants' exposure in genetically defined subgroups of mother-infant pairs: an observational study

Clin Infect Dis. 2015 Aug 1;61(3):453-63. doi: 10.1093/cid/civ317. Epub 2015 Apr 16.


Background: The antiretroviral drug efavirenz is widely used during breastfeeding. Evaluating its safety requires an understanding of its breast milk pharmacokinetics, level of breastfed infants' exposure, and potential influence of polymorphisms in drug disposition genes.

Methods: For this observational study, we investigated plasma and breast milk pharmacokinetics of efavirenz and breastfed infants' exposure in human immunodeficiency virus positive nursing mothers and their breastfed infants. We also evaluated potential variability due to genetic polymorphisms in CYP2B6, NR1I3, CYP2A6, ABCB1, ABCB5, and ABCG2.

Results: CYP2B6 516G>T was independently associated with efavirenz concentrations in maternal plasma, breast milk, and infant plasma (n = 134). When stratified based on CYP2B6 516G>T (n = 29 ; 11 GG, 10 GT and 8 TT), efavirenz pharmacokinetic parameters in plasma and breast milk differed significantly between patient groups. The median time-averaged milk-to-plasma concentration ratio was 1.10 (range: 0.57-1.71). The estimated maximum infant efavirenz dose from breast milk was 809 µg/kg/day (215-2760) and pediatric dose weight-adjusted exposure index was 4.05% (1.08-13.8). Infant plasma concentrations did not change significantly during the dosing interval, 157 ng/mL (28.6-1360) in pooled analysis and 315 ng/mL (108-1360) in CYP2B6 516TT group. Infant plasma concentrations were highest up to 8 days of age at 1590 ng/mL (190-4631) and decreased by about 90% in the age stratum day 9 to 3 months. No efavirenz related toxicity was reported.

Conclusions: Most breastfed infants are exposed to <10% of the weight-adjusted therapeutic pediatric dose, the safety threshold for exposure to maternal drugs from breast milk.

Keywords: CYP2B6 516G>T; breast milk; efavirenz; infant exposure; pharmacokinetics.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alkynes
  • Anti-HIV Agents / analysis*
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Benzoxazines / analysis*
  • Benzoxazines / blood
  • Benzoxazines / pharmacokinetics*
  • Benzoxazines / therapeutic use
  • Breast Feeding
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6 / genetics
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Linear Models
  • Milk, Human / chemistry*
  • Milk, Human / metabolism
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide / genetics
  • Young Adult


  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6
  • efavirenz