About this webinar
Determining the amount of drug transferred into human milk is critical for the benefit-risk analysis of taking medications while breastfeeding. Although a clinical lactation study is recommended by the US Food and Drug Administration (FDA) to assess the extent of drug transfer into milk and support drug labeling, it is challenging to enroll lactating women. Currently available in vitro methods don’t adequately predict drug transfer into milk to support risk assessment and drug labeling. To fill the knowledge gap, the presenter’s group developed an in vitro-in vivo extrapolation (IVIVE) approach to predict human milk/plasma (M/P) drug concentration ratios.
In this webinar, the presenter will introduce the new IVIVE approach and compared its prediction performance with five literature in vitro prediction approaches. Drug unionized fractions at pH 7.0 and 7.4, protein/lipids binding in human plasma and milk, and Caco-2 or MDCK cell permeability in both directions were incorporated into the developed IVIVE model. A total of 71 drugs with published bilateral Caco-2 permeability data were used to test our IVIVE model. Compared with five in vitro prediction approaches reported in literature, the developed IVIVE approach provides a more accurate prediction of drug M/P ratios, especially for passive-diffusion drugs. The predictions for transporter substrates need further improvement, especially for the substrates of apical transporter (P-gp, MATEs and MCT-1).
The presenter will also introduce the mechanisms of therapeutic antibody transfer from human blood to milk and review currently available human lactation data for FDA-approved therapeutic antibodies. The relationships between M/P ratio of therapeutic antibodies and FcRn binding affinity/elimination half-life were also tentatively investigated.
- Describe the factors which affect drug or biologic transfer from a lactating woman’s blood to milk.
- Discuss current challenges in human M/P ratio prediction, especially for transporter substrates.
- Idenifty the IVIVE model for the prediction of M/P ratios for small-molecule drugs.
- Assess potential risks to infants caused therapeutic biologics excreted into human milk.