Drugs in human milk. Clinical pharmacokinetic considerations.
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.
Atkinson
H C
HC
Department of Clinical Pharmacology, Christchurch Hospital.
Begg
E J
EJ
Darlow
B A
BA
D001942:Breast Feeding; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008895:Milk, Human / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics; D011247:Pregnancy
D004364:Pharmaceutical Preparations