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Distribution of R ‐ and S ‐methadone into human milk during multiple, medium to high oral dosing
Author(s) -
Begg Evan J.,
Malpas Timothy J.,
Hackett L. Peter,
Ilett Kenneth F.
Publication year - 2001
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.0306-5251.2001.01506.x
Subject(s) - methadone , dosing , medicine , pharmacokinetics , methadone maintenance , zoology , anesthesia , pharmacology , biology
Aims To measure the interdose milk to plasma ratio (M/P) of R‐ and S‐ methadone during multiple dosing in lactating mothers taking medium to high doses of methadone (> 40 mg daily), and to assess likely infant exposure. Methods Eight mother/child pairs were studied, initially during their postpartum hospital stay (immature milk), and where possible again after 15 days (mature milk). The women were on a methadone maintenance programme with daily doses of ≥40 mg day −1 . Venous blood was collected at 0, 1, 2, 4, 6, 8, 12, and 24 h and milk was collected from both breasts at 0–4, 4–8, 8–12, 12–16, 16–20, and 20–24 h after dose . R‐ and S‐ methadone were quantified by h.p.l.c. The areas under the plasma and milk concentration‐time curves (AUC) were estimated and M/P AUC was calculated. The relative infant dose of both enantiomers was estimated as the product of drug concentration in milk and an average daily milk intake of 0.15 l kg −1 . Results For immature milk ( n = 8) the M/P AUC for R‐ methadone was 0.68 (95% CI 0.48, 0.89) and for S ‐methadone 0.38 (0.26, 0.50). For mature milk ( n = 2) the M/P AUCs for R ‐methadone were 0.39 and 0.54 and for S‐ methadone 0.24 and 0.30, respectively. The estimated doses of R ‐ and S‐ methadone that would be received by the infant via immature milk were 3.5% (2.05, 5.03%) and 2.1% (1.3, 2.8%), respectively, of the maternal dose (assuming 50% of each enantiomer in the dose). The relative infant dose for R‐ plus S‐ methadone together was 2.8% (1.7, 3.9%). Conclusions Breastfeeding during medium to high dose methadone appears to be ‘safe’ according to conventional criteria because the dosage is < 10%. However because the absolute dose received by the infant is dependent on the maternal dose rate, the risk‐benefit ratio should be considered for each individual case. The doses of methadone received via milk are unlikely to be sufficient to prevent the neonatal abstinence syndrome.