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SummaryWarfarin was measured with a sensitive and specific method in the plasma and breast milk of 13 mothers.Less than 0-08 [tmol warfarin per litre (25 ng/ml) of breast milk was found in each instance. Seven of the mothers were breast-feeding their infants, in none of whom was warfarin detected in the plasma; furthermore, in three the British corrected ratio of the plasma was appreciably less than that of the mother and was within the expected range. We conclude that nursing mothers given warfarin may safely breast-feed their infants. IntroductionNursing mothers given anticoagulants by mouth are often advised against breast-feeding because of the risk of transferring the drug to the infant. More mothers are now seeking advice about this because of the widespread use of oral anticoagulants post partum and because of the increased popularity of breastfeeding.This problem has been investigated previously, but for several reasons there is little consensus on whether oral anticoagulants are present in breast milk. Firstly, the standard of clinical documentation in many reports leaves much to be desired.

Drugs may interact with warfarin through pharmacodynamic or pharmacokinetic mechanisms. Examples of the former include alteration of the bioavailability of vitamin K by antibiotics, mineral oils or cholestyramine; oestrogens, diuretics and hypolipidaemic agents such as clofibrate may influence vitamin K-dependent clotting factor synthesis, and drugs which affect haemostasis, e.g. via platelet function, will enhance the anticoagulant effect of warfarin. Pharmacokinetic interactions are better understood. Few drugs have been shown to alter warfarin absorption, the importance of protein binding displacement has been exaggerated, and since warfarin is not eliminated to any extent unchanged by the kidney, the most important kinetic interactions are those due to inhibition or induction of its hepatic metabolism. Isomeric differences in metabolism form an important basis for stereoselective metabolic interactions, especially inhibition; this has been demonstrated with phenylbutazone, metronidazole and co-trimoxazole. Enzyme induction, although recognised for many years, may still pose problems in therapeutics, usually on withdrawal of the inducing agent.

1 The effects on heart rate and blood pressure after single and multiple dosing (1 month) of a long acting formulation of propranolol 160 mg daily, and conventional propranolol, 80 mg twice daily, or 160 mg daily were compared in 11 moderately hypertensive subjects previously shown to respond to propranolol.2 After acute dosing all three treatments produced significant reduction in blood pressure. After multiple dosing all three treatments maintained significant reductions in lying, standing and exercise heart rate and blood pressure throughout the 24 h. At24 h, after multiple dosing, the fall in resting and standing systolic BP was significantly greater with LA propranolol than with conventional propranolol 80 mg twice daily or conventional propranolol 160 mg once daily (P at least < 0.05). 3 The plasma propranolol concentration time curve after LA propranolol showed slowed absorption, and the area under the curve was significantly lower than after conventional propranolol (acute dosing; LA propranolol 160 mg 560 mg ml-l h, conventional propranolol 80 mg twice daily 1135 mg ml-l h, conventional propranolol 160 mg daily 1414 mg ml-l h).

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