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

Department of Anesthesiology, Flemish Free University of Brussels, Brussels, Belgium.

Abstract

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 ₁-acid glycoprotein (₁-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 (f_1/2ß), volume of distribution at steady state (Vd_ss), and total plasma clearance (Cl_p) 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 ₁-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 ₁-AGP concentration and the bound to free alfentanil fraction (f_b/f_u). 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 ₁-AGP levels, a larger free alfentanil fraction existed in neonates.

Key Words: ANALGESICS—alfentanil • ANESTHESIA, OBSTETRIC • PHARMACOKINETICS—alfentanil

This article has been cited by other articles:

				P. K. Morley-Forster, D. W. Reid, and H. Vandeberghe A comparison of patient-controlled analgesia fentanyl and alfentanil for labour analgesia Can J Anesth, February 1, 2000; 47(2): 113 - 119. [Abstract] [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999