Distribution of R- and S-methadone into human milk during multiple, medium to high oral dosing

E.J. Begg, T.J. Malpas, L.P. Hackett, Kenneth Ilett

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Abstract

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 (miniature milk), and where possible again after 15 days (mature milk). The women were on a methadone maintenance programme with daily doses of greater than or equal to 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 I kg(-1).Results For miniature 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/PAUC, 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 miniature milk, were 3.5% (2.05, 5.03%) and 2.1% (13, 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.
Original languageEnglish
Pages (from-to)681-685
JournalBritish Journal of Clinical Pharmacology
Volume52
DOIs
Publication statusPublished - 2001

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