Excretion of dothiepin and its primary metabolites in breast milk

Kenneth Ilett, T.H. Lebedevs, R.E. Wojnar-Horton, M.J. Roberts, L.J. Dusci, L.P. Hackett, P. Yapp

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    38 Citations (Scopus)

    Abstract

    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 <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-mu-g l-1) while in four others both dothiepin-S-oxide and nordothiepin-S-oxide were below their minimum quantifiable levels (10-mu-g 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.
    Original languageEnglish
    Pages (from-to)635-639
    JournalBritish Journal of Clinical Pharmacology
    Volume33
    DOIs
    Publication statusPublished - 1992

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