Aims Methadone is widely used in maintenance programs for opioid-dependent subjects. The aims of the study were to quantify the distribution and excretion of methadone in human milk during the early postnatal period and to investigate exposure of breast fed infants to the drug. Methods Blood and milk samples were obtained from 12 breast feeding women who were taking methadone in daily doses ranging from 20-80 mg (0.3-1.14 mg kg −1 ). Blood was also obtained from eight of their infants. Methadone concentration in these samples was quantified by h.p.l.c. The infants were observed for withdrawal symptoms.Results The mean (95% CI) milk/plasma ratio was 0.44 (0.24-0.64). Exposure of the infants, calculated assuming an average milk intake of 0.15 l kg −1 day −1 and a bioavailability of 100% was 17.4 (10.8-24) mg kg. The mean infant dose expressed as a percentage of the maternal dose was 2.79 (2.07-3.51)%. Methadone concentrations in seven infants were below the limit of detection for the h.p.l.c. assay procedure, while one infant had a plasma methadone concentration of 6.5 mg l −1 . Infant exposure to methadone via human milk was insufficient to prevent the development of a neonatal abstinence syndrome which was seen in seven (64%) infants. No adverse effects attributable to methadone in milk were seen. Conclusions We conclude that exposure of breast fed infants to methadone taken by their mothers is minimal and that women in methadone maintenance programs should not be discouraged from breast feeding because of this exposure.

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Aims To characterise milk/plasma (M/P) ratio and infant exposure, for sertraline and N-desmethylsertraline, in breast-feeding women taking sertraline for the treatment of depression. Methods Eight women (mean age 28 years) taking sertraline (1.05 mg kg −1 day −1 ) and their infants (mean age 5.7 months) were studied. Sertraline and Ndesmethylsertraline in plasma and milk were measured by high-performance liquid chromatography over a 24 h dose interval at steady-state. M/P values were estimated from area under the plasma and milk concentration-time curves. All milk produced was collected over the dose interval. Infant exposure was estimated as the product of actual or estimated milk production, and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. Results Mean milk production was 321 ml day −1 (range 34-974 ml). Mean M/P values of 1.93 and 1.64 were calculated for sertraline and N-desmethylsertraline respectively. Infant exposure estimated from actual milk produced was 0.2% and 0.3% of the weight-adjusted maternal dose for sertraline and N-desmethylsertraline (as sertraline equivalents) respectively. When calculated from estimated milk production (0.15 l kg −1 day −1 ), infant exposure was significantly greater ( P<0.0001) at 0.90% and 1.32% for sertraline and N-desmethylsertraline respectively. Neither sertraline nor its N-desmethyl metabolite could be detected in plasma samples from the four infants tested. No adverse effects were observed in any of the eight infants and all had achieved normal developmental milestones. Conclusions Irrespective of the method of calculation of infant exposure, the mean total dose of sertraline and its N-desmethyl metabolite transmitted to infants via breast-feeding is low and unlikely to cause any significant adverse effects.Keywords: sertraline, N-desmethylsertraline, human milk, infant dose abstract outlining a study of nine subjects [6]. Comprehensive Introduction characterisation of the transfer of drugs into human milk involves the measurement of milk/plasma (M/P) distribution Depression affects some 3 to 12% of the population each year, and is approximately twice as frequent in women as ratio and the average concentration of drug in milk over a dose interval [7]. Ideally, these data should be obtained by men [1,2]. The rate of new psychiatric episodes in women increases markedly in the first 3 months after childbirth, measurement of areas under the milk and plasma concentration-time curves (AUC) at steady state [8]. Using this with between 10 and 15% of mothers experiencing depression [3]. Sertraline is a derivative of naphthylamine experimental design, the present study measured M/P ratios and mean infant exposure for sertraline and its major that belongs to the selective serotonin (5-HT) reuptake inhibitor (SSRI) group of antidepressants [4]. The SSRIs metabolite N-desmethylsertraline. are being prescribed increasingly for the treatment of postnatal depression, posing a dilemma for mothers wh...

1 The excretion of a 6 mg subcutaneous dose of sumatriptan in breast milk was studied in five lactating volunteer subjects with a mean age of 27.6 years and a mean body weight of 75 kg. Drug concentrations in milk and plasma over the ensuing 8 h were measured by high‐performance liquid chromatography. 2 The mean milk:plasma ratio estimated from the areas under the milk and plasma concentration‐time curves (AUC) was 4.9 (95% CI 4.1–5.7), indicating a significant transfer of sumatriptan into the milk compartment. 3 The mean total recovery of drug in milk was estimated to be only 14.4 μg (95% CI 6.1–22.7 μg), or 0.24% of the 6 mg administered dose. On a weight‐adjusted basis this corresponded to a mean infant exposure of 3.5% of the maternal dose (95% CI 0.3–6.7%). 4 If oral bioavailability in the infant is similar to that in adults (14%), the weight‐adjusted infant dose is reduced to 0.49%. Furthermore, allowance for reduced clearance in the infant predicts an infant exposure varying from 4.9% in a very premature neonate to 0.7% in a 30 week old infant. 5 Since sumatriptan is usually administered as a single dose at infrequent intervals, the low level of excretion in breast milk suggests that continued breast feeding following its use will not pose a significant risk to the suckling infant. Even this minor exposure could be largely avoided by expressing and discarding all milk for 8 h after the dose.

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