Pharmacokinetic characteristics of fentanyl iontophoretic trandermal system over a range of applied current

Abstract

Objective: To evaluate the pharmacokinetic (PK) characteristics of a modified fentanyl iontophoretic transdermal system (ITS).

Research design and methods:This was a prospective, open-label, single-center, randomized, 3-period, 5-treatment, 6-sequence study. Each subject was randomly assigned to receive three treatments in a sequence consisting of intravenous fentanyl citrate, fentanyl ITS at 170 μA, and then one of three other fentanyl ITS treatments at 140, 200 or 230 μA.

Main outcome measures: The following PK parameters were determined: C_max, t_max, t_1/2, AUC_{23 – 25} and amount of fentanyl absorbed into systemic circulation (i.e., Dose Absorbed).

Results: Fifty-two subjects received at least one fentanyl treatment. Serum exposure (C_max and AUC_{23 – 25}) and Dose Absorbed increased with increasing current. The median t_max ranged from 23.0 to 23.2 h across the 4 ITS groups. Mean t_1/2 values ranged from 11.0 to 13.0 h. The Dose Absorbed from the fentanyl ITS at 170 μA met bioequivalence criteria when compared to data from an earlier version of the fentanyl ITS.

Conclusions: Exposure of fentanyl and the amount of fentanyl absorbed increased with the magnitude of applied current with the ITS. The fentanyl ITS at 170 μA is bioequivalent to an earlier version of the system.

Keywords:

• fentanyl
• iontophoretic transdermal system
• patient-controlled analgesia
• pharmacokinetic

Acknowledgements

The authors gratefully acknowledge Kirsten Reimen (InClin) for assistance with planning and execution of this study and Starr Grundy (SD Scientific) for editorial assistance. Results of this study were presented in part at the Annual Meeting of the International Anesthesia Research Society (May 17-20, 2014; Montréal, Canada).

Declaration of interest

Study funding was provided by Incline Therapeutics, Inc., a wholly owned subsidiary of The Medicines Company (Parsippany, NJ). The analyses and writing of this manuscript were supported financially by The Medicines Company. Brad Phipps and Nitin Joshi are employees of The Medicines Company. Raymond S Sinatra is Acting Director of Pain Medicine at the West Haven VA Medical Center, West Haven CT, and serves as a consultant to The Medicines Company. Kelly Regal and Jinfang Li are employees of ProPharma Services and provided PK and statistical analysis services to Incline Therapeutics.

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