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

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 postpa...

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Bibliographic Details
Published in:British journal of clinical pharmacology 2001-12, Vol.52 (6), p.681-685
Main Authors: Begg, Evan J., Malpas, Timothy J., Hackett, L. Peter, Ilett, Kenneth F.
Format: Article
Language:English
Subjects:
Administration, Oral
Adolescent
Adult
Analgesics, Opioid - administration & dosage
Analgesics, Opioid - blood
Analgesics, Opioid - pharmacokinetics
Area Under Curve
Biological and medical sciences
Breast Feeding
Dose-Response Relationship, Drug
enantiomers
Female
Humans
Infant, Newborn
Medical sciences
methadone
Methadone - administration & dosage
Methadone - blood
Methadone - pharmacokinetics
milk
Milk, Human - chemistry
Milk, Human - metabolism
Miscellaneous
pharmacokinetics
Pharmacology. Drug treatments
Stereoisomerism
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Summary: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/PAUC 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/PAUC 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/PAUCs 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
ISSN:0306-5251
1365-2125
DOI:10.1046/j.0306-5251.2001.01506.x