Literature DB >> 18294329

Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk.

Kenneth F Ilett1, Michael J Paech, Madhu Page-Sharp, Sherwin K Sy, Judith H Kristensen, Raymond Goy, Sebastian Chua, Tracey Christmas, Karen L Scott.   

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: There are presently no published data on tramadol transfer into breast milk or on its effects in the breastfed infant. WHAT THIS STUDY ADDS: We have provided quantitative data on the absolute and relative infant doses of rac-tramadol and it rac-O-desmethyl metabolite for the breastfed infant. We have also demonstrated a novel sparse sampling data collection method for investigating infant exposure via milk. AIMS: To investigate the transfer of rac-tramadol and its rac-O-desmethyl metabolite into transitional milk, and assess unwanted effects in the breastfed infant.
METHODS: Tramadol HCl (100 mg six hourly) was administered to 75 breastfeeding mothers for postoperative analgesia on days 2-4 after Caesarian section. Milk and plasma samples were collected after administration of four or more doses. Rac-tramadol and rac-O-desmethyltramadol were measured by high performance liquid chromatography. Milk : plasma ratio (M : P) and infant doses were calculated by standard methods. The behavioural characteristics of the exposed breastfed infants and a matched control group of infants not exposed to tramadol were also studied. RESULTS At steady-state, mean (95% CI) M : P was 2.2 (2.0, 2.4) for rac-tramadol and 2.8 (2.5, 3.1) for rac-O-desmethyltramadol. The estimated absolute and relative infant doses were 112 (102, 122) microg kg(-1) day(-1) and 30 (28, 32) microg kg(-1) day(-1), and 2.24% (2.04, 2.44)% and 0.64% (0.59, 0.69)% for rac-tramadol and rac-O-desmethyltramadol, respectively. The exposed infants and control breastfed infants had similar characteristics, including Apgar scores at birth and Neurologic and Adaptive Capacity Scores.
CONCLUSIONS: The combined relative infant dose of 2.88% at steady-state was low. The similarity of NACS in exposed infants and controls suggests that there were no significant behavioural adverse effects. We conclude that short-term maternal use of tramadol during establishment of lactation is compatible with breastfeeding.

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Year:  2008        PMID: 18294329      PMCID: PMC2432475          DOI: 10.1111/j.1365-2125.2008.03117.x

Source DB:  PubMed          Journal:  Br J Clin Pharmacol        ISSN: 0306-5251            Impact factor:   4.335


  17 in total

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