Relationship between human milk lipid-ultrafiltrate and octanol-water partition coefficients.

The distribution into human milk lipid of 16 drugs with widely varying lipophilicity is reported. There is a high degree of correlation between milk lipid-ultrafiltrate and octanol-water partition coefficients, measured at 37 degrees C, provided digoxin and prednisolone are excluded. These steroid-based molecules may interact with free fatty acids in milk, forming micelles and thus perturbing the milk lipid-ultrafiltrate relationship. Equations are described which enable estimation of drug distribution into milk for lipid-soluble drugs, based on drug pKa and octanol-water partition coefficients.