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.
The microbial degradation of cholic acid by Pseudomonas sp. N.C.I.B. 10590 was studied, and two major products were isolated and identified as 7 alpha, 12 beta-dihydroxyandrosta-1,4-diene-3,17-dione and 7 alpha, 12 alpha-dihydroxy-3-oxopregna-1,4-diene-20-carboxylic acid. Four minor products were isolated and evidence is given for the following structures: 7 alpha, 12 alpha-dihydroxyandrosta-1,4-diene-3,17-dione, 12 beta-hydroxyandrosta-1,4,6-triene-3,17-dione, 7 alpha, 12 beta, 17 beta-trihydroxyandrosta-1,4-dien-3-one and 7 alpha, 12 alpha-dihydroxy-3-oxopregn-4-ene-20-carboxylic acid. The significance of the production of the steroid products is discussed, along with the possible enzymic mechanisms responsible for their production.
A method has been developed for single ion monitoring of diphenylhydantoin and its major metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin in plasma. A plasma extract is reacted with N,O-bis(trimethylsilyl) acetamide and single ion recording is carried out using a gas chromatograph mass spectrometer system. The mass value selected, m/e 254, is common to the TMS ethers of diphenylhydantoin and its principal metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin. The result indicate that one cause of an adverse reaction to diphenylhydantoin could be a reduced ability to hydroxylate the drugmquantitative methods for the analysis of the drug and its major metabolite have also been developed. Diphenylhydantoin and 5-(p-hydroxyphenyl)-5-phenylhydantoin can be analysed in plasma after addition of deuterium labelled internal standards and conversion to volatile derivatives for mass fragmentographic analysis. Diphenylhydantoin and its internal standard are analysed as the N,N-dimethyl derivative, and the hydroxylated metabolite and its internal standard are converted to a petrimethylsilyl compound by reaction with N,O-bis-(trimethylsilyl)acetamide.
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