Pharmacokinetics and transplacental distribution of fentanyl in epidural anesthesia for normal pregnant women

Abstract

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. PATIENTS and 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 tricompartmental model. The fetal/maternal ratio of the plasma fentanyl was determined at birth. RESULTS: The values of the pharmacokinetic parameters were: t_½α = 13.5 min, t_1/2β = 192.5 min, t_1/2γ = 620 min, AUC^0-∞ = 137.404 ng.min per millilter, 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. CONCLUSION: 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.