PLASMA AND BREAST-MILK CONCENTRATIONS OF DOTHIEPIN AND NORTHIADEN IN LACTATING WOMEN

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) mug/l and 72(+/- 79) mug/l respectively while breast-milk concentrations were 95(+/- 71) mug/l and 40(+/- 29) mug/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.