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Pharmacokinetics and Placental Transfer of Intravenous and Epidural Alfentanil in Parturient Women

1986; Lippincott Williams & Wilkins; Volume: 65; Issue: 11 Linguagem: Inglês

10.1213/00000539-198611000-00010

1526-7598

E. Gepts, Luc Heytens, F. Camu,

Cardiac, Anesthesia and Surgical Outcomes

Alfentanil was administered as a 30 μg/kg single intravenous injection to five healthy women scheduled for elective cesarean section (group A). In five pregnant women normal vaginal delivery was supported by epidural analgesia with a 30 μg/kg loading dose followed by a 30 μg/kg−1/hr−1 infusion of alfentanil (group B). Five healthy nonpregnant women scheduled for minor general surgery received 120 μg/kg alfentanil intravenously as a bolus before surgical incision (group C). In groups A and B plasma alfentanil concentrations, alfentanil plasma protein binding, and α1-acid glycoprotein (α1-AGP) Concentrations were measured in maternal and umbilical arterial or uenous blood samples at delivery. Multiple arterial sampling in groups A and C for measurement of alfentanil plasma concentration decay analysis indicated three-compartmental characteristics in most patients. In the pregnant population terminal half-life (f1/2β), volume of distribution at steady state (Vdss), and total plasma clearance (Clp) amounted to 103 ± 67 min, 541 ± 155 mllkg and 6.48 ± 0.85 ml/kg−1/mm1, respectively (mean ± SD), and did not differ significantly in nonpregnant patients. In groups A and B the fetal-maternal ratios indicated a concentration gradient for the total plasma alfentanil content (ratio of total alfentanil concentrations in umbilical venous and maternal blood (UJM), 0.31 ± 0.08 and 0.28 ± 0.06 (mean ± SD) in groups A and B respectively) with a larger protein binding capacity in maternal plasma (group A, 85 ± 3%; group B, 90 ± 1%) (mean ± SD). The concentration of α1-AGP, the most important binding protein for alfentanil, was significantly lower in umbilical venous blood (22 ± 7 mg/100 ml) (mean ± SD) than in the maternal samples (group A, 42 ± 5 mg/100 m1; group B, 55 ± 13 mg/100 ml) (mean ± SD). A positive correlation was observed between the plasma alfentanil concentrations of total alfentanil and free alfentanil in the mothers and neonates, as well as between the α1-AGP concentration and the bound to free alfentanil fraction (fb/fu). Thus the intravenous pharmacokinetics of a bolus dose of alfentanil are not significantly altered in late pregnancy. Free alfentanil easily crossed the placental barrier. Because of decreased fetal α1-AGP levels, a larger free alfentanil fraction existed in neonates.