Answer:
Size of the drug molecule
Maternal plasma concentration
Degree of ionisation
Step-by-step explanation:
Size of the drug molecule
Most drug molecules, including alcohol, nicotine and caffeine, are small enough to enter milk. Exceptions are drugs with high molecular weights such as heparins and insulin.
Maternal plasma concentration
Passive diffusion is the primary pathway by which drugs enter milk. There is a good concordance between the time-course of maternal plasma-drug concentration and milk-drug concentration. Maternal plasma concentration is also affected by the drug’s distribution into different tissues. A high volume of distribution (as for sertraline) will contribute to a lower maternal plasma concentration and a subsequent lower concentration in milk.
Degree of ionisation
Drugs cross membranes in an un-ionised form. Milk is generally slightly more acidic (pH 7.2) than the mother’s plasma (pH 7.4) so it attracts weak organic bases such as oxycodone and codeine.7 Such drugs become ionised and ‘trapped’ in the milk. Conversely, weak organic acids such as penicillin tend to be ionised and held in maternal plasma.