Court, Richard, Gausi, Kamunkhwala, Mkhize, Buyisile, Wiesner, Lubbe, Waitt, Catriona 
ORCID: 0000-0003-0134-5855, McIlleron, Helen, Maartens, Gary, Denti, Paolo and Loveday, Marian
(2022)
Bedaquiline exposure in pregnancy and breastfeeding in women with rifampicin-resistant tuberculosis.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 88 (8).
pp. 3548-3558.
|
Text
Brit J Clinical Pharma - 2022 - Court - Bedaquiline exposure in pregnancy and breastfeeding in women with.pdf - Published version Download (1MB) | Preview |
Abstract
<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | breastfeeding, pharmacokinetics, pregnancy |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 10 Jun 2022 08:25 |
| Last Modified: | 19 Oct 2023 04:02 |
| DOI: | 10.1111/bcp.15380 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3156159 |
Dimensions
Dimensions
