Generally, adult glomerular filtration rates (adjusted for the difference in surface area) are attained by five to six months of age.
Metabolic processes such as phase 1 oxidation and phase 2 glucuronidation are also impaired in the neonate.
Factors such as the dose received via breast milk, and the pharmacokinetics and effect of the drug in the infant need to be taken into consideration.
Problems should not be overstated however, as many drugs are considered 'safe' during breastfeeding.
Milk composition varies within and between feeds and this may also affect transfer of drugs into breast milk.
For example, milk at the end of a feed (hindmilk) contains considerably more fat than foremilk and may concentrate fat-soluble drugs.
However, the risk to the infant must be considered in relation to the toxicity of the drug used, the dosage regimen and the area of application.
For example, use of corticosteroids nasal sprays or inhalers in standard doses would be considered compatible with breastfeeding.
Within a few days of delivery, term infants have glomerular filtration rates approximately one-third of adult values after adjusting for difference in body surface area, and premature infants have even more impaired clearance (see Table 1).
Drugs such as lithium (infant dose as high as 80% of the weight-adjusted maternal dose) and amiodarone (infant dose up to 50%) should be avoided due to high infant exposure and potential for significant toxicity.
For drugs with greater inherent toxicity such as cytotoxic agents, ergotamine, gold salts, immunosuppressives and isotretinoin, the cut-off of 10% is too high and breastfeeding is contraindicated.
Transfer of drugs into breast milk is most commonly described quantitatively using the milk to plasma (M/P) concentration ratio.
The accuracy of this value is improved if it is based on the area under the concentration-time curves (AUC) of the drug in maternal milk and plasma (M/P (L/kg/day) The volume of milk ingested by infants is commonly estimated as 0.15L/kg/day.Drugs subject to high first-pass metabolism may have higher oral availability in premature or term infants due to impaired ability to metabolise on first-pass.