Bedaquiline exposure in pregnancy and breastfeeding in women with rifampicin‐resistant tuberculosis

AIMS: We aimed to explore the effect of pregnancy on bedaquiline pharmacokinetics (PK) and describe bedaquiline exposure in the breast milk of mothers treated for rifampicin‐resistant tuberculosis (TB), where there are no human data available. METHODS: We performed a longitudinal PK study in pregnant women treated for rifampicin‐resistant TB to explore the effect of pregnancy on bedaquiline exposure. Pharmacokinetic sampling was performed at 4 time‐points over 6 hours in the third trimester, and again at approximately 6 weeks postpartum. We obtained serial breast milk samples from breastfeeding mothers, and a single plasma sample taken from breastfed and nonbreastfed infants to assess bedaquiline exposure. We used liquid chromatography–tandem mass spectrometry to perform the breast milk and plasma bedaquiline assays, and population PK modelling to interpret the bedaquiline concentrations. RESULTS: We recruited 13 women, 6 of whom completed the ante‐ and postpartum PK sampling. All participants were HIV‐positive on antiretroviral therapy. We observed lower ante‐ and postpartum bedaquiline exposures than reported in nonpregnant controls. Bedaquiline concentrations in breast milk were higher than maternal plasma (milk to maternal plasma ratio: 14:1). A single random plasma bedaquiline and M2 concentration was available in 4 infants (median age: 6.5 wk): concentrations in the 1 breastfed infant were similar to maternal plasma concentrations; concentrations in the 3 nonbreastfed infants were detectable but lower than maternal plasma concentrations. CONCLUSION: We report low exposure of bedaquiline in pregnant women treated for rifampicin‐resistant TB. Bedaquiline significantly accumulates in breast milk; breastfed infants receive mg/kg doses of bedaquiline equivalent to maternal doses.