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

Abstract

Alfentanil was administered as a 30 micrograms/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 micrograms/kg loading dose followed by a 30 micrograms/kg-1/hr-1 infusion of alfentanil (group B). Five healthy nonpregnant women scheduled for minor general surgery received 120 micrograms/kg alfentanil intravenously as a bolus before surgical incision (group C). In groups A and B plasma alfentanil concentrations, alfentanil plasma protein binding, and alpha 1-acid glycoprotein (alpha 1-AGP) concentrations were measured in maternal and umbilical arterial or venous 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 (t1/2 beta), volume of distribution at steady state (Vdss), and total plasma clearance (Clp) amounted to 103 +/- 67 min, 541 +/- 155 ml/kg and 6.48 +/- 0.85 ml/kg-1/min-1, 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 (Uv/M), 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).(ABSTRACT TRUNCATED AT 250 WORDS)