NEUROLEPTIC DRUGS IN BREAST-MILK - A STUDY OF PHARMACOKINETICS AND OFPOSSIBLE ADVERSE-EFFECTS IN BREAST-FED INFANTS

Background. Very little is known about the pharmacokinetics of neurole ptic drugs in breast-feeding mothers and their infants or about possib le adverse effects in the infants. Method. Twelve mothers who breast-f ed their infants were prescribed haloperidol, chlorpromazine or triflu operazine. 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 sens itive EIA. Repeated clinical and developmental assessments of the brea st-fed infants were carried out up to 30 months of age. The control su bjects were 18 bottle-fed infants whose mothers were also prescribed n euroleptic or mood-stabilizing drugs. Results. The total concentration s of neuroleptic drugs and their principal metabolites in maternal pla sma were correlated with concentrations in fore-milk. Infants were ing esting up to 3% of the maternal daily dose per kg body weight and smal l amounts of the drugs were detected in infants' plasma and urine. Con centrations of haloperidol in the adult range were found in plasma fro m 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 moth ers were prescribed both haloperidol and chlorpromazine showed a decli ne in their developmental scores from the first to the second assessme nt at 12-18 months. Conclusion. More extensive longitudinal studies ar e needed but, in the meantime, there appears to be grounds for caution if breast-feeding mothers are prescribed doses of single or two neuro leptic drugs at the upper end of their recommended ranges.