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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

Abstract


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.


Keywords


fentanyl, matrix, transdermal, pharmacokinetics, drug delivery

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References


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.




DOI: https://doi.org/10.5055/jom.2011.0052

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