Prediction of milk/plasma concentration ratio of drugs.
OBJECTIVE
The milk to plasma (m/p) concentration ratio of drugs is used to estimate the amount of drug offered to the suckling infant. Published literature was reviewed to identify drugs for which sufficient data exist for calculation of m/p ratio and to examine whether the existing empiric data agree with the published method of Atkinson for mathematical prediction of m/p ratios based on physiochemical characteristics.


METHODS
Using a comprehensive reference text, we identified studies reporting sufficient data to calculate m/p ratio based on the AUC for milk and plasma. Subsequently, we calculated the m/p ratio with Atkinson's formula based on pKa, lipophilicity, and protein binding. We then correlated the empiric versus predicted (calculated) m/p ratios.


RESULTS
Of 192 drugs of which at least some data on milk accumulation have been published, there were sufficient data to quantify m/p ratios for only 69 medications (78 studies). There was no significant correlation between the empiric m/p ratios and the predicted values using the Atkinson's model.


CONCLUSIONS
Reliable data on m/p concentration ratios exist for few medications. Presently, there is no appropriate model to predict milk concentrations of drugs in humans.
Larsen
Line Alleslev
LA
The Motherisk Program, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Ito
Shinya
S
Koren
Gideon
G
D019540:Area Under Curve; D005260:Female; D006801:Humans; D007774:Lactation / Q000378:metabolism*; D008895:Milk, Human / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000097:blood* / Q000378:metabolism*; D010599:Pharmacokinetics
D004364:Pharmaceutical Preparations