No abstract

This open-label, parallel study of 28 men was conducted to evaluate the pharmacokinetics and safety of fentanyl delivered by the E-TRANS (fentanyl) electrotransport transdermal system (ALZA Corporation, Palo Alto, CA). The E-TRANS (fentanyl) system provided electrically assisted, transdermal, continuous delivery of fentanyl. Treatments consisted of no current (group A); a constant current of 100 microA for 26 hours plus 4 additional doses at varying currents for varying times during hour 25 (groups B, C, D); a constant current of 100 microA for 26 hours plus 4 additional doses at 1,200 microA over 2.5 minutes during hour 1 (group E); or 500 microA for 0.5 hours and 100 microA for 3.5 hours (group F). No fentanyl was detected in serum when no current had been applied. Mean serum fentanyl concentrations were similar regardless of current duration during hour 25 (treatments B, C, D). Increases in mean serum fentanyl concentrations were significantly lower during additional dosing for treatment E compared with treatments B, C, and D. Serum fentanyl concentrations sufficient for analgesia (1-3 ng/mL) were attained in treatments using the E-TRANS (fentanyl) system with basal current of 100 microA for 26 hours. There were no safety issues after treatment with E-TRANS (fentanyl) system with concurrent opioid antagonist (naltrexone) administration. The only adverse event requiring treatment was a headache (n = 1). The majority of subjects had no or barely perceptible erythema at the application site 24 hours after system removal. Application of E-TRANS (fentanyl) resulted in therapeutically significant serum fentanyl concentrations over a range of applied currents. Overall serum fentanyl concentrations were higher when the skin had been primed by constant-current fentanyl delivery.

Alfentanil disposition after an intravenous bolus of 50 micrograms/kg was followed in 15 elderly surgical patients and was compared to that in nine young adults. A two-compartment open model described alfentanil disappearance from plasma. Apparent volumes of distribution of the central compartment (201 and 211 ml/kg; means), at steady state (460 and 543 ml/kg), and of the AUC (746 and 722 ml/kg) in young adults and in elderly subjects did not differ. Plasma clearance was lower in elderly subjects (4.4 ml/min/kg) than in young adults (6.5 ml/min/kg), whereas terminal plasma t1/2 was longer in the elderly patients (137 and 83 min). Alfentanil dosage should therefore be reduced in elderly patients when large single doses, multiple doses, or long-term infusions are required.

Summary

Maternal and umbilical venous plasma was obtained at delivery from 8 mothers and their neonates after an i.v. bolus injection of alfentanil, and from 6 mothers and their neonates after epidural administration of sufentanil. Plasma levels of total (free + bound) alfentanil in neonates were about 3.4-times lower than in their mothers. At 33-55 min after 30 micrograms sufentanil, total drug levels in mothers were around the limit of detection of the radioimmunoassay (0.05 ng/ml); in one mother who had received 250 micrograms, the plasma level of total sufentanil was 2.6-times higher than in her neonate. Plasma protein binding of alfentanil was 88.2% in mothers and 67.2% in neonates. Plasma protein binding of sufentanil was 90.7% in mothers and 79.3% in neonates. For both drugs, plasma protein binding was significantly related to the alpha 1-acid glycoprotein (alpha 1-AGP) level, which was about 2.5-times lower in the infants. Free alfentanil levels in mothers and neonates were similar. Free levels of sufentanil in mothers and neonates differed less from each other than did the total drug levels.