Plasma and breast milk concentrations of dothiepin and northiaden in lactating women

Abstract Plasma and breast‐milk concentrations of dothiepin and its metabolite northiaden were measured in 20 lactating women receiving the drug for post‐partum depression. Samples were collected at steady‐state and both compounds quantitated by HPLC. Doses of dothiepin varied from 75 mg/day to 225 mg/day. Accordingly a wide range of plasma and breast‐milk concentrations of dothiepin and northiaden were determined. Most determinations were made for women receiving 150 mg/day. At this dose mean (± SD) plasma concentrations of dothiepin and northiaden were 56(±27)m̈g/l and 72(±79)m̈g/l respectively while breast‐milk concentrations were 95(±71) m̈g/l and 40(±29) m̈g/l for dothiepin and northiaden respectively. The data reflect the well recognised inter‐individual variability in plasma concentrations for subjects receiving the same oral dose. Similar variability was noted in breast‐milk concentrations at all doses of dothiepin. Dothiepin passes into the breast‐milk of lactating women receiving the drug for post‐partum depression. In this respect the drug is similar to other tricyclic antidepressants. The inter‐individual variability of results recorded here suggest the need to determine drug concentrations on an individual basis before reaching a decision about breastfeeding. Perceived side effects in the infant are clear criteria for cessation of breastfeeding; high levels of drug in breastmilk where the infant is unaffected, warrant monitoring in view of our inadequate knowledge regarding long term effects of these drugs.