Pharmacokinetics and transplacental distribution of fentanyl in epidural anesthesia for normal pregnant women.
BACKGROUND
Fentanyl is an opioid drug widely used as a co-adjuvant in abdominal delivery, a fact that justifies its pharmacokinetic study under these conditions.


OBJECTIVE
Our objective was to investigate the pharmacokinetics and placental transfer of fentanyl in parturients whose pregnancies were resolved by cesarian section with epidural anesthesia.


METHODS
Ten clinically normal parturients who delivered at term received 5 ml of 2% lidocaine hydrochloride without a vasoconstrictor for skin and subcutaneous blockade, followed by epidural injection of 2 ml fentanyl citrate (0.05 mg/ml), 15 ml 0.5% bupivacaine hydrochloride with 1:200,000 epinephrine, and 10 ml 2% lidocaine hydrochloride without a vasoconstrictor. Maternal blood samples were collected at various times after injection (1--840 min), and the fentanyl plasma concentrations were determined by gas chromatography-mass spectrometry. Pharmacokinetic analysis was performed using the bi- or tri-compartmental model. The fetal/maternal ratio of the plasma fentanyl was determined at birth.


RESULTS
The values of the pharmacokinetic parameters were: t(1/2)alpha=13.5 min, t(1/2)beta=192.5 min, t(1/2)gamma=620 min, AUC(0-infinity)=137.404 ng.min per milliliter, C(l)/f=464.984 ml/min, V(d)/f=299.974 l, C(l)/f/kg=6.875 ml/min per kilogram, and V(d)/f/kg=4.441 l/kg. The latency between drug administration and birth was 28.5 min, with a maternal and fetal plasma concentration of 0.310 and 0.245 ng/ml, respectively, at a median fetal/maternal ratio of 0.892.


CONCLUSIONS
The study demonstrated a rapid passage of fentanyl from the epidural space to maternal blood and a significant transplacental transfer of maternal fentanyl of about 90%, which should serve as an alert to obstetricians.
Moisés
Elaine Christine Dantas
EC
Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirão Preto, University Hospital, University of São Paulo, Ribeirão Preto, Brazil.
de Barros Duarte
Luciana
L
de Carvalho Cavalli
Ricardo
R
Lanchote
Vera Lúcia
VL
Duarte
Geraldo
G
da Cunha
Sérgio Pereira
SP
D015360:Analgesia, Epidural; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D000701:Analgesics, Opioid; D005283:Fentanyl