OII-C-4Midazolam elimination in human breast milk

Abstract

BACKGROUND Lactating women undergoing operations under general anesthesia are advised to pump and discard their milk for 24h after the procedure. We determined the kinetics of midazolam elimination in breast milk to ascertain its safety after midazolam administration. METHODS Five lactating women were studied after providing institutionally-approved written informed consent. Patients were premedicated with midazolam, 2 mg IV, 5 min before anesthetic induction with fentanyl, 100 μg IV, and propofol, 2.5 mg/kg IV. Anesthesia was maintained with potent volatile anesthetics. Milk was collected using an electric breast pump before and at 5, 7, 9, 11, and 24h after drug administration. Blood samples were collected before and at regular intervals up to 7h after drug administration. Plasma and milk midazolam concentrations were measured by LC-MS. Midazolam elimination in milk was modelled simultaneously with the plasma kinetics as the cumulative amount of drug in milk just as urinary elimination is modelled, albeit with a delay. RESULTS Plasma midazolam pharmacokinetics were consistent with those reported by ourselves and others. In 24h of milk collection, only 0.005 (± 0.005)% of the midazolam dose was eliminated in milk, representing 0.009 (± 0.005)% of the midazolam elimination clearance with a pharmacokinetic delay of approximately 9h. CONCLUSION The amount of midazolam appearing in breast milk over 24h after administering a single dose is very small and unlikely to affect a healthy term infant. Clinical Pharmacology & Therapeutics (2005) 79, P7–P7; doi: 10.1016/j.clpt.2005.12.021