Effect of Current Density on Pharmacokinetics Following Continuous or Intermittent Input from a Fentanyl Electrotransport System†

doi:10.1021/js970437d

Journal of Pharmaceutical Sciences

Volume 87, Issue 8, August 1998, Pages 976-981

https://doi.org/10.1021/js970437d Get rights and content

Abstract

The pharmacokinetics of fentanyl were determined in two open-label crossover studies following 24-h periods of delivery by an electrotransport transdermal system (E-TRANS [fentanyl] system) in young healthy male volunteers. A direct current was applied continuously in study 1 (at 50, 100, and 200 μA; surface area = 5 cm²; n = 8), but in study 2 it was limited to the first 20 min of each hour (at 150, 200, and 250 μA; surface area = 2 cm²; n = 12). The opioid effects of fentanyl were blocked with naltrexone administered every 12 h. With increasing electrical current, the increase in serum fentanyl concentration, amount absorbed, and AUC values were proportional in study 2 but not in study 1. It is hypothesized that the lack of proportionality in study 1 is due to lower current density (μA/cm²) in this study. It appears that for fentanyl, the current density should be about 75 μA/cm² or greater for a linear relation between current and amount absorbed as seen in study 2. Compared with intravenously infused fentanyl, the serum concentrations resulting from E-TRANS (fentanyl) system application revealed a slightly dampened rate of increase (stratumcorneum barrier effect) and decrease in serum concentrations, and a similar intersubject variability in fentanyl AUC values. Fentanyl pharmacokinetics with either E-TRANS (fentanyl) or intravenous infusion were time-invariant over a 24-h application period, with similar mean half-life values (about 15–18 h). E-TRANS (fentanyl) administration (either continuous or intermittent input) was safe and well tolerated. Adverse effects were mild to moderate; they consisted mainly of local erythema and pruritus (which resolved in most patients within 24 h after system removal) and occasional opioid effects.

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^☆: This work was performed at Inveresk Clinical Research Ltd, Edinburgh, Scotland.

^‡: ALZA Corp.

^§: Janssen Pharmaceutica.

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Research ArticlesEffect of Current Density on Pharmacokinetics Following Continuous or Intermittent Input from a Fentanyl Electrotransport System†☆

Abstract

J. Pharm. Sci.

Transdermal Iontophoretic Delivery of Therapeutic Peptides/Proteins (I) Insulin

Transdermal Delivery of Drugs by Iontophoresis: A Review

Drug Des. Delivery

Pulsatile drug delivery from electrotransport therapeutic systems

Research Articles
Effect of Current Density on Pharmacokinetics Following Continuous or Intermittent Input from a Fentanyl Electrotransport System^†☆