Open Access Open Access  Restricted Access Subscription or Fee Access

Bioequivalence and safety of a novel fentanyl transdermal matrix system compared with a transdermal reservoir system

Kenneth Todd Moore, MS, Holly D. Adams, MS, Jaya Natarajan, PhD, Jay Ariyawansa, MS, Henry M. Richards, MD


Objectives: Fentanyl is a potent synthetic opioid used for the management of chronic pain. A newer transdermal matrix system was developed and compared with a reservoir system used in the United States.
Setting: An open-label, single-center, randomized, two-period crossover study was conducted to evaluate the bioequivalence of the transdermal matrix system to the transdermal reservoir system. Seventy-four subjects completed treatment with both the reservoir system (100 μg/h) and the matrix system (100 μg/h), each applied for 72 hours. After application of the first system, subjects completed a 9-day washout and then crossed over to receive the other system for another 72 hours.
Main outcome measure: Blood samples for the determination of serum fentanyl concentrations were taken in each treatment period for up to 120 hours following application.
Results: The ratios of geometric means for maximum fentanyl concentration (Cmax) and area under the concentration-time curve (AUClast and AUC∞ ) were 106 percent, 110 percent, and 110 percent, respectively. The 90% confidence intervals for the ratios of the geometric means were contained within the bioequivalence criteria of 80-125 percent. The matrix system adhered well to skin. Systemic and topical safety profiles were comparable between treatments.
Conclusions: The transdermal fentanyl matrix system adhered well, was well tolerated, and produced systemic exposures of fentanyl that were bioequivalent to the reservoir system.


fentanyl, matrix, transdermal, pharmacokinetics, drug delivery

Full Text:



Muijsers RB, Wagstaff AJ: Transdermal fentanyl: An updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control. Drugs. 2001; 61(15): 2289-2307.

Grond S, Radbruch L, Lehmann KA: Clinical pharmacokinetics of transdermal opioids: Focus on transdermal fentanyl. Clin Pharmacokinet. 2000; 38(1): 59-89.

Varvel JR, Shafer SL, Hwang SS, et al.: Absorption characteristics of transdermally administered fentanyl. Anesthesiology. 1989; 70(6): 928-934.

Mather LE: Clinical pharmacokinetics of fentanyl and its newer derivatives. Clin Pharmacokinet. 1983; 8(5): 422-446.

McClain DA, Hug CC Jr: Intravenous fentanyl kinetics. Clin Pharmacol Ther. 1980; 28(1): 106-114.

Peng PW, Sandler AN: A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology. 1999; 90(2): 576-599.

Hug CC Jr, Murphy MR: Tissue redistribution of fentanyl and termination of its effects in rats. Anesthesiology. 1981; 55(4): 369-375.

Meuldermans WE, Hurkmans RM, Heykants JJ: Plasma protein binding and distribution of fentanyl, sufentanil, alfentanil and lofentanil in blood. Arch Int de Pharmacodyn Ther. 1982; 257(1): 4-19.

Goromaru T, Matsuura H, Yoshimura N, et al.: Identification and quantitative determination of fentanyl metabolites in patients by gas chromatographyÑMass spectrometry. Anesthesiology. 1984; 61(1): 73-77.

Labroo RB, Paine MF, Thummel KE, et al.: Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: Implications for interindividual variability in disposition, efficacy, and drug interactions. Drug Metab Dispos. 1997; 25(9): 1072-1080.

Andrews CJH, Prys-Roberts C: Fentanyl: A review. Clin Anesthesiol. 1983; 1(1): 97-122.

Lilleng PK, Mehlum LI, Bachs L, et al.: Deaths after intravenous misuse of transdermal fentanyl. J Forensic Sci. 2004; 49(6): 1364-1366.

Kuhlman JJ Jr, McCaulley R, Valouch TJ, et al.: Fentanyl use, misuse, and abuse: A summary of 23 postmortem cases. J Anal Toxicol. 2003; 27(7): 499-504.

Arvanitis ML, Satonik RC: Transdermal fentanyl abuse and misuse. Am J Emerg Med. 2002; 20(1): 58-59.

Reeves MD, Ginifer CJ: Fatal intravenous misuse of transdermal fentanyl. Med J Aust. 2002; 177(10): 552-553.

Marquardt KA, Tharratt RS, Musallam NA: Fentanyl remaining in a transdermal system following three days of continuous use. Ann Pharmacother. 1995; 29(10): 969-971.

Phipps B, Cormier M, Gale B, et al.: Transdermal drug delivery. In Wnek GE, Bowlin GL (eds.): Encyclopedia of Biomaterials and Biomedical Engineering. 2nd ed. New York: Marcel Dekker, Inc., 2008: 2893-2905.

Sathyan G, Guo C, Sivakumar K, et al.: Evaluation of the bioequivalence of two transdermal fentanyl systems following single and repeat applications. Curr Med Res Opin. 2005; 21(12): 1961-1968.

Lehmann KA, Zech D: Transdermal fentanyl: Clinical pharmacology. J Pain Symptom Manage. 1992; 7(3 Suppl): S8-S16.

Marier JF, Lor M, Potvin D, et al.: Pharmacokinetics, tolerability, and performance of a novel matrix transdermal delivery system of fentanyl relative to the commercially available reservoir formulation in healthy subjects. J Clin Pharmacol. 2006; 46(6): 642-653.

Marier JF, Lor M, Morin J, et al.: Comparative bioequivalence study between a novel matrix transdermal delivery system of fentanyl and a commercially available reservoir formulation. Br J Clin Pharmacol. 2007; 63(1): 121-124.

Miyazaki T, Hanaoka K, Namiki A, et al.: Efficacy, safety and pharmacokinetic study of a novel fentanyl-containing matrix transdermal patch system in Japanese patients with cancer pain. Clin Drug Investig. 2008; 28(5): 313-325.

Kress HG, Boss H, Delvin T, et al.: Transdermal fentanyl matrix patches Matrifen and Durogesic DTrans are bioequivalent. Eur J Pharm Biopharm. 2010; 75(2): 225-231.



  • There are currently no refbacks.