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PEDIATRICS

Prediction of Milk/Plasma Concentration Ratio of Drugs

at time of writing, International Summer Student, The Motherisk Program, The Hospital for Sick Children, University of Toronto, Toronto, Canada; now, Pharmacist, School of Pharmacy, Copenhagen, Denmark

Shinya Ito, MD

Pediatrician and Clinical Pharmacologist, The Motherisk Program; Director, Division of Clinical Pharmacology, The Hospital for Sick Children, University of Toronto

Gideon Koren, MD FABMT FRCPC

Director, The Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto; Pediatrician and Clinical Pharmacologist, Senior Scientist, The Canadian Institutes for Health Research, holder of the Research Leadership in Better Pharmacotherapy During Pregnancy and Lactation, Toronto

Reprints: Gideon Koren MD FABMT FRCPC, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, 555 University Ave., Toronto M5G 1X8, Ontario, Canada, FAX 416/813-7562, gkoren{at}sickkids.ca

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 Atkinsonís 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 Atkinsonís 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.

Key Words: breast milk, drug concentration

Published Online, August 1, 2003. www.theannals.com, DOI 10.1345/aph.1C379

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