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

Kenneth F. Ilett, Michael J. Paech, Madhu Page-Sharp, Sherwin K. Sy, Judith H. Kristensen, Raymond Goy, Sebastian Chua, Tracey Christmas & Karen L. Scott
British Journal of Clinical Pharmacology Volume 65, Issue 5, Date: May 2008, Pages: 661-666


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) μg kg−1 day−1 and 30 (28, 32) μg 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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