TY - JOUR
T1 - Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk
AU - Ilett, Kenneth
AU - Paech, Mike
AU - Page-Sharp, M.
AU - Sy, S.K.
AU - Kristensen, J.H.
AU - Goy, R.
AU - Chua, S.
AU - Christmas, T.
AU - Scott, K.L.
PY - 2008
Y1 - 2008
N2 - AIMSTo investigate the transfer of rac-tramadol and its rac-O-desmethyl metabolite into transitional milk, and assess unwanted effects in the breastfed infant.METHODSTramadol 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.RESULTSAt 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) mu g kg(-1) day(-1) and 30 (28, 32) mu g 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.CONCLUSIONSThe 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.
AB - AIMSTo investigate the transfer of rac-tramadol and its rac-O-desmethyl metabolite into transitional milk, and assess unwanted effects in the breastfed infant.METHODSTramadol 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.RESULTSAt 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) mu g kg(-1) day(-1) and 30 (28, 32) mu g 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.CONCLUSIONSThe 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.
U2 - 10.1111/j.1365-2125.2008.03117.x
DO - 10.1111/j.1365-2125.2008.03117.x
M3 - Article
VL - 65
SP - 661
EP - 666
JO - British Journal Clinical Pharmacology
JF - British Journal Clinical Pharmacology
SN - 0306-5251
IS - 5
ER -