Pharmacokinetics of midazolam, propofol, and fentanyl transfer to human breast milk

BACKGROUND AND OBJECTIVES: Lactating women undergoing operations requiring general anesthesia are advised to pump and discard their milk for 24 hours after the procedure. Data on anesthetic drug transfer into breast milk are limited. This study determined the pharmacokinetics of midazolam, propofol, and fentanyl transfer into milk to provide caregivers with data regarding the safety of breast milk after administration of these drugs. METHODS: Five lactating women participated in this study after providing institutionally approved written informed consent. Patients underwent premedication with midazolam before induction of anesthesia with propofol and fentanyl. Anesthesia was maintained with a potent volatile anesthetic. Milk and blood were collected before drug administration. Milk was collected 5, 7, 9, 11, and 24 hours after drug administration. Venous blood was collected at intervals up to 7 hours. Plasma and milk midazolam, propofol, and fentanyl concentrations were measured by HPLC with tandem mass spectrometric or fluorescence detection. The pharmacokinetics of drug transfer into milk was modeled with plasma pharmacokinetics. RESULTS: Plasma midazolam, propofol, and fentanyl pharmacokinetics were consistent with reports of others. In 24 hours of milk collection, averages of 0.005% (range, 0.002%-0.013%) of the maternal midazolam dose, 0.027% (0.004%-0.082%) of the propofol dose, and 0.033% (0.006%-0.073%) of the fentanyl dose were collected in milk, representing averages of 0.009%, 0.025%, and 0.039% of the respective elimination clearances. CONCLUSION: The amount of midazolam, propofol, and fentanyl excreted into milk within 24 hours of induction of anesthesia provides insufficient justification for interrupting breast-feeding.