The excretion of dothiepin and its primary metabolites in breast milk.

1. The excretion of dothiepin, nordothiepin, dothiepin‐S‐oxide and nordothiepin‐S‐oxide into breast milk was studied in eight women. Exposure to drug was measured in five of their infants, and possible drug‐related effects were assessed in all eight infants. 2. Using pre‐ feed milk samples mean (+/‐ s.e. mean) milk:plasma (M:P) ratios were 0.78 +/‐ 0.12, 0.85 +/‐ 0.16, 1.18 +/‐ 0.29 and 1.86 +/‐ 0.29 for dothiepin, nordothiepin, dothiepin‐S‐oxide and nordothiepin‐S‐oxide, respectively. In post‐feed milk samples, the mean M:P ratio for dothiepin (1.59 +/‐ 0.32) was significantly greater (P less than 0.05) but M:P ratios for the metabolites were similar. 3. Mean total calculated infant daily doses, (in dothiepin equivalents and as a percent of the maternal dose) were 0.58% for dothiepin, 0.23% for nordothiepin, 2.47% for dothiepin‐S‐oxide, and 1.17% for nordothiepin‐S‐ oxide. 4. Plasma samples were obtained from five infants. In one, both dothiepin and nordothiepin were below their minimum quantifiable levels (2 micrograms l‐1) while in four others both dothiepin‐S‐oxide and nordothiepin‐S‐oxide were below their minimum quantifiable levels (10 micrograms l‐1). No adverse effects were found in any of the eight infants. 5. Use of dothiepin by depressed mothers is unlikely to be a significant hazard to their breast‐feeding infants.

DOI: 10.1111/j.1365-2125.1992.tb04093.x

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