Drug distribution within human milk phases.

Phase distribution and protein binding of drugs in human milk have been measured. The analytical method is reproducible, rapid, and requires only small sample volumes. Five drugs were studied: diazepam, phenobarbital, warfarin, phenytoin, and disopyramide. Experiments were carried out at 37 degrees C on milk samples with variable fat and protein contents. Results for the distribution of drugs between the skimmed-milk phase and fat-rich phase are presented, as well as the results of the dialysis of drugs in skimmed milk. It is shown that, among the physicochemical properties of a drug, the lipid solubility seems to be the most important property for predicting variations in drug concentrations in milk. The potential significance of the findings with respect to in vivo distribution of drugs into human milk is discussed.