When studying drugs during lactation the investigator must consider the balance and relationship between mother, breast milk, and the breast-fed child. The optimal study would evaluate all three components (e.g., mother—infant pairs); however, in some circumstances other designs can be useful (e.g., maternal milk) and may need to be performed before a mother-infant pair study is conducted. Other potential designs include only those lactating women studies which provide data on the PK of the drug in lactating women and the amount of drug transferred into breast milk. Alternatively, only women studies that provide data exclusively on milk may verify other studies (e.g., in vitro data) that predict drug transfer in human milk. In some circumstances the study of milk alone may preceed more intensive investigation utilizing mother-infant pairs.
In general mother-infant pair studies should measure the amount of drug and metabolites transferred into breast milk, characterize the PK of the drug in lactating women, and assess drug exposure in the breast-fed child via breast milk. This design would include frequent maternal blood and milk samples that are simultaneously obtained and carefully timed. This design would also include infant sampling of blood and/or urine and would encourage alternative noninvasive pediatric sampling strategies (e.g., saliva, tears) to reliably determine drug levels and PK parameter estimates in infants.
Clinical lactation studies could be nested within a larger clinical study on safety or efficiacy outcomes or conducted in combination with the postpartum assessment of the effects of pregnancy on PK/PD of a drug. Information obtained from single-dose studies are useful and may be more acceptable to volunteers and aid in recruitment; however, the normal therapeutic practice (e.g., dose, frequency, and route of administration) should be considered in the study design. When drugs are normally taken in repeated doses, studies performed at steady state are encouraged. For probe substrates for drug metabolism studies drugs a single dose could be given.
As with pregnancy study designs, a multiple-arm design could be used. For drugs that are given acutely (e.g., single dose or short course of therapy) it may be difficult to use a longitudinal design with the same patients throughout lactation. If there is a concern that the effects of drug use in lactation differ based upon the stage of lactation, or the postpartum status, a multiple-arm design could be considered. Each woman could serve as her own control and have PK/PD determinations performed once during lactation and after weaning is complete.
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