Drugs in human milk. Clinical pharmacokinetic considerations
- PMID: 3292101
- DOI: 10.2165/00003088-198814040-00003
Drugs in human milk. Clinical pharmacokinetic considerations
Abstract
Drugs ingested by a lactating mother would be expected to appear in human milk to some extent and be ingested by a breast-feeding infant. Drugs pass from maternal plasma into milk by passive diffusion and are distributed within the aqueous, protein and lipid phases of milk. Distribution into milk will be affected by physiochemical characteristics of the drug: acid-base characteristics, relative protein binding in plasma and milk, and lipid solubility, as well as milk composition. The milk-to-plasma concentration ratio is the most commonly quoted index of drug distribution into human milk. However, calculation of the daily infant dose of drug ingested in milk, and from this the dose in milk relative to the maternal dose on a weight-adjusted basis, is a more relevant indicator of infant exposure to a drug. This is particularly true for drugs with a high volume of distribution, for which only a small proportion of the mother's dose is contained within the plasma and available for distribution into milk. A better indication of infant exposure to a drug is the steady-state plasma drug concentration in a breast-feeding infant, the major determinants of which are the dose rate (via milk) and the oral availability and clearance in the infant. Although in neonates the rate of absorption may be different from adults, there is little evidence that its extent is significantly different. Clearance, however, is impaired in very young infants, particularly if premature. The decreased clearance would result in a proportional increase in steady-state plasma concentrations in the breast-feeding infant. Consideration of the dose ingested in milk and the approximate clearance in infants of different ages allows estimation of likely steady-state plasma concentrations in breast-feeding infants. From these considerations, recommendations regarding the safety of drugs during breast-feeding can be made. Drugs which are very toxic or have dose-independent toxicity should be considered separately. Recommendations regarding 'social' drugs such as nicotine, alcohol, caffeine and theobromine are particularly difficult, as doses are uncontrolled and vary variable.
Similar articles
-
The effect of medications on the lactating mother and her infant.Clin Obstet Gynecol. 1980 Dec;23(4):1073-80. doi: 10.1097/00003081-198012000-00010. Clin Obstet Gynecol. 1980. PMID: 6160936 Review.
-
A novel index for expressing exposure of the infant to drugs in breast milk.Br J Clin Pharmacol. 1994 Aug;38(2):99-102. doi: 10.1111/j.1365-2125.1994.tb04331.x. Br J Clin Pharmacol. 1994. PMID: 7981020 Free PMC article.
-
Partitioning of drugs into human milk.Ann Acad Med Singap. 1991 Jan;20(1):51-5. Ann Acad Med Singap. 1991. PMID: 2029164 Review.
-
Drugs and breast feeding.Semin Perinatol. 1979 Jul;3(3):271-8. Semin Perinatol. 1979. PMID: 42981 Review.
-
Transfer of olanzapine into breast milk, calculation of infant drug dose, and effect on breast-fed infants.Am J Psychiatry. 2003 Aug;160(8):1428-31. doi: 10.1176/appi.ajp.160.8.1428. Am J Psychiatry. 2003. PMID: 12900304
Cited by
-
Use of sodium aurothiomalate during lactation.Br J Clin Pharmacol. 1990 Jun;29(6):777-9. doi: 10.1111/j.1365-2125.1990.tb03703.x. Br J Clin Pharmacol. 1990. PMID: 2116162 Free PMC article.
-
Antipsychotics and breast-feeding: a review of the literature.Paediatr Drugs. 2000 Jan-Feb;2(1):23-8. doi: 10.2165/00148581-200002010-00003. Paediatr Drugs. 2000. PMID: 10937456 Review.
-
Prediction of drug concentrations in milk during breastfeeding, integrating predictive algorithms within a physiologically-based pharmacokinetic model.CPT Pharmacometrics Syst Pharmacol. 2021 Aug;10(8):878-889. doi: 10.1002/psp4.12662. Epub 2021 Jul 2. CPT Pharmacometrics Syst Pharmacol. 2021. PMID: 34213088 Free PMC article.
-
Clinical pharmacokinetics of non-opiate abused drugs.Clin Pharmacokinet. 1989 Jan;16(1):1-26. doi: 10.2165/00003088-198916010-00001. Clin Pharmacokinet. 1989. PMID: 2565176 Review.
-
Excretion of azapropazone in human breast milk.Eur J Clin Pharmacol. 1990;39(3):271-3. doi: 10.1007/BF00315109. Eur J Clin Pharmacol. 1990. PMID: 2257865
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical