Yoshida K, Smith B, Craggs M, Kumar R
Section of Perinatal Psychiatry, University of London.
Psychol Med. 1998 Jan;28(1):81-91. doi: 10.1017/s0033291797005965.
Very little is known about the pharmacokinetics of neuroleptic drugs in breast-feeding mothers and their infants or about possible adverse effects in the infants.
Twelve mothers who breast-fed their infants were prescribed haloperidol, chlorpromazine or trifluoperazine. Two methods, enzyme immunoassay (EIA) and high performance liquid chromatography (HPLC) were used to assay these drugs in samples from mothers, but infants' samples were assayed only by the more sensitive EIA. Repeated clinical and developmental assessments of the breast-fed infants were carried out up to 30 months of age. The control subjects were 18 bottle-fed infants whose mothers were also prescribed neuroleptic or mood-stabilizing drugs.
The total concentrations of neuroleptic drugs and their principal metabolites in maternal plasma were correlated with concentrations in fore-milk. Infants were ingesting up to 3% of the maternal daily dose per kg body weight and small amounts of the drugs were detected in infants' plasma and urine. Concentrations of haloperidol in the adult range were found in plasma from 2 of 5 infants assayed by EIA but there was no evidence of any acute or delayed adverse effects. Three other breast-fed infants whose mothers were prescribed both haloperidol and chlorpromazine showed a decline in their developmental scores from the first to the second assessment at 12-18 months.
More extensive longitudinal studies are needed but, in the meantime, there appears to be grounds for caution if breast-feeding mothers are prescribed doses of single or two neuroleptic drugs at the upper end of their recommended ranges.
关于抗精神病药物在母乳喂养母亲及其婴儿体内的药代动力学，以及对婴儿可能产生的不良反应，人们所知甚少。
给12名母乳喂养婴儿的母亲开了氟哌啶醇、氯丙嗪或三氟拉嗪。采用酶免疫测定法（EIA）和高效液相色谱法（HPLC）两种方法测定母亲样本中的这些药物，但婴儿样本仅通过更灵敏的EIA进行测定。对母乳喂养的婴儿进行了长达30个月的反复临床和发育评估。对照组为18名人工喂养婴儿，其母亲也被开了抗精神病或心境稳定剂药物。
母亲血浆中抗精神病药物及其主要代谢物的总浓度与初乳中的浓度相关。婴儿每千克体重摄入的药物量高达母亲日剂量的3%，且在婴儿血浆和尿液中检测到少量药物。通过EIA检测的5名婴儿中有2名的血浆中发现了成人范围内的氟哌啶醇浓度，但没有任何急性或延迟不良反应的证据。另外3名母乳喂养婴儿的母亲同时被开了氟哌啶醇和氯丙嗪，在12至18个月时，从第一次评估到第二次评估，他们的发育得分有所下降。
需要进行更广泛的纵向研究，但与此同时，如果给母乳喂养的母亲开单种或两种抗精神病药物的剂量达到推荐范围上限，似乎有理由谨慎行事。
