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


CONCLUSIONS
The amount of midazolam, propofol, and fentanyl excreted into milk within 24 hours of induction of anesthesia provides insufficient justification for interrupting breast-feeding.
Nitsun
Martin
M
Department of Anesthesiology, Evanston Northwestern Healthcare, Evanston, IL 60611-3008, USA.
Szokol
Joseph W
JW
Saleh
H Jacob
HJ
Murphy
Glenn S
GS
Vender
Jeffery S
JS
Luong
Lynn
L
Raikoff
Kiril
K
Avram
Michael J
MJ
D000328:Adult; D000768:Anesthesia, General; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001942:Breast Feeding / Q000009:adverse effects; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007774:Lactation; D008874:Midazolam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008895:Milk, Human / Q000378:metabolism*; D015742:Propofol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D018686:Anesthetics, Intravenous; D008874:Midazolam; D005283:Fentanyl; D015742:Propofol