Models and methods for predicting drug transfer into human milk.

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Pediatric Pharmacology
• Toxicology

Background:

• Infant exposure to drugs and xenobiotics via breast milk is a significant safety concern.
• The milk to plasma concentration ratio (M/P) is a critical parameter for quantifying infant drug exposure.
• In vivo human M/P data is lacking for most drugs, necessitating reliable prediction methods.

Purpose of the Study:

• To review and evaluate existing methods for predicting the milk to plasma concentration ratio (M/P) in humans.
• To assess the utility, advantages, and disadvantages of different M/P prediction approaches.
• To guide the selection of appropriate methods for estimating infant drug exposure through breast milk.

Main Methods:

• In vitro studies using mammary cell monolayers.
• Assessment of drug binding to plasma and milk proteins and lipids.
• In vivo animal experiments.
• Regression modeling based on physicochemical properties of compounds.

Main Results:

• The article provides a comprehensive review of various M/P prediction methodologies.
• Each method's strengths and limitations in predicting human M/P are discussed.
• No single method is universally sufficient; a combination is often required.

Conclusions:

• Accurate prediction of the milk to plasma concentration ratio (M/P) is essential for infant safety.
• A combination of in vitro, in vivo, and in silico methods offers the most reliable approach for human M/P prediction.
• Further research and validation of predictive models are needed to ensure infant well-being.