Pharmacokinetics of Drugs Used to Treat Drug-sensitive Tuberculosis in Breastfeeding Mother-infant Pairs: An Observational Pharmacokinetic Study

Background

Worldwide, ~50% of women take medication during breastfeeding. Data surrounding the exposure of the breastfed infant to drugs and any associated risks are sparse. Despite longstanding recommendations from the US Food and Drug Administration (FDA) for lactation studies to be performed close to licensing for drugs anticipated to be widely used in women of childbearing age, such studies are rarely undertaken. Drugs taken by the breast feeding mother on TB treatment can be passed from the maternal circulation to the milk and then to the breastfed infant, a concern of effects of anti-tuberculosis drugs on nursing infants. Most TB drugs are metabolized by the liver, triggering a potential risk of drug accumulation in infants due to their immature liver function particularly in premature infants.

Drugs are transferred to milk in small quantities, and many have been used without obvious infant toxicity for many years hence the large gaps in the data. Pharmacokinetic (PK) information of anti- TB drugs transfer to breast milk and breastfed infant is crucial to limit the development of drug resistance and understand the safety of prolonged exposure through breast milk.

Problem Statement

Whilst data on TB drug penetration into breastmilk is limited, information on clinically relevant infant exposure to TB drug-sensitive is even more limited and is an important knowledge gap both for safety, and because therapeutic concentrations could be 1) protective in exposed infants, obviating the need for TB preventive therapy or 2) sub- therapeutic concentrations could select for resistance in those infants infected with Mycobacterium tuberculosis.