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Clinical Pharmacokinetics

, Volume 45, Issue 8, pp 843–850 | Cite as

Comparison of Equivalent Doses of Fentanyl Buccal Tablets and Arteriovenous Differences in Fentanyl Pharmacokinetics

  • Mona DanvishEmail author
  • Mary Kirby
  • Philmore RobertsonJr
  • Edward Hellriegel
  • John G. Jiang
Original Research Article

Abstract

Background

The fentanyl buccal tablet (FBT) is designed to enhance the rate and extent of fentanyl absorption through the buccal mucosa.

Aim

To evaluate the bioequivalence of μg-equivalent doses of FBT administered as single and multiple tablets and assess differences in the arterial and venous pharmacokinetics of FBT in healthy volunteers.

Methods

Twenty-seven healthy adults, aged 19–5 years, participated in the randomised, open-label, three-period, crossover study. In the first two periods, FBT was administered as four 100μg tablets simultaneously or one FBT 400μg to assess bioequivalence. Venous blood samples were obtained over a 72-hour period to measure plasma fentanyl concentrations. In the third period, arterial and venous blood samples were obtained simultaneously from before administration of one FBT 400μg through 4 hours after administration to evaluate the impact of arterial versus venous sampling on the pharmacokinetic profile. As subjects were not opioid tolerant, naltrexone was administered to block opioid receptor-mediated effects of fentanyl. Adverse events were recorded throughout.

Results

Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinity (AUC) on average were approximately 12% and 13% higher, respectively, for FBT administered as four 100μg tablets simultaneously compared with one FBT 400μg. Maximum plasma concentrations in the arterial circulation were approximately 60% higher and occurred 15 minutes earlier than those measured from the venous circulation. No serious adverse events were reported during the study.

Conclusion

Despite small differences in Cmax and AUC (on average 12% and 13%, respectively), FBT administered as four 100μg tablets simultaneously compared with one 400μg tablet did not meet the criteria for bioequivalence. An increased surface area exposure with four tablets compared with one tablet may account for the slightly higher maximum concentrations observed with four 100μg tablets. A substantially higher Cmax was reached earlier in the arterial than in the venous circulation.

Keywords

Fentanyl Naltrexone Venous Sampling Breakthrough Pain Arterial Circulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study was supported by Cephalon, Inc. (Frazer, PA, USA). The authors are employed by the sponsoring company and have no other financial interests or conflicts of interest to disclose. The authors would also like to thank James C. Kisicki, MD and the staff at MDS Pharma Services (Lincoln, NE, USA) for help in carrying out this study.

References

  1. 1.
    Bennett D, Burton A, Fishman S, et al. Consensus panel recommendations for the assessment and management of breakthrough pain. Part 2: management. Pharm Ther 2005; 30(6): 354–61Google Scholar
  2. 2.
    Pather SI, Siebert JM, Hontz J, et al. Enhanced buccal delivery of fentanyl using the OraVescent drug delivery system. Drug Deliv Tech 2001; 1(1): 54–7Google Scholar
  3. 3.
    Eichman JD, Robinson JR. Mechanistic studies on effervescent-induced permeability enhancement. Pharm Res 1998; 15(6): 925–30PubMedCrossRefGoogle Scholar
  4. 4.
    Eichman JD, Yassin AEB, Robinson JR. The influence of in-vivo carbonation on GI physiological processes and drug permeability. Eur J Pharm Biopharm 1997; 44: 33–8CrossRefGoogle Scholar
  5. 5.
    Durfee S, Messina J, Khankari RK. Fentanyl effervescent buccal tablets: enhanced buccal absorption. Am J Drug Deliv 2006; 4(1): 1–5CrossRefGoogle Scholar
  6. 6.
    Hudson RJ, Thomson IR, Cannon JE, et al. Pharmacokinetics of fentanyl in patients undergoing abdominal aortic surgery. Anesthesiology 1986; 64(3): 334–8PubMedCrossRefGoogle Scholar
  7. 7.
    Hug Jr CC, Murphy MR. Tissue redistribution of fentanyl and termination of its effects in rats. Anesthesiology 1981; 55(4): 369–75PubMedCrossRefGoogle Scholar
  8. 8.
    Boer F, Bovill JG, Burm AG, et al. Uptake of sufentanil, alfentanil and morphine in the lungs of patients about to undergo coronary artery surgery. Br J Anaesth 1992; 68(4): 370–5PubMedCrossRefGoogle Scholar
  9. 9.
    Chiou WL. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Part I). Clin Pharmacokinet 1989; 17(3): 175–99PubMedCrossRefGoogle Scholar
  10. 10.
    Hill HF, Chapman CR, Saeger LS, et al. Steady-state infusions of opioids in human: II. Concentration-effect relationships and therapeutic margins. Pain 1990; 43(1): 69–79PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Mona Danvish
    • 1
    Email author
  • Mary Kirby
    • 1
  • Philmore RobertsonJr
    • 2
  • Edward Hellriegel
    • 2
  • John G. Jiang
    • 3
  1. 1.Clinical PharmacologyCephalon, Inc.FrazerUSA
  2. 2.Drug Safety and DispositionCephalon, Inc.FrazerUSA
  3. 3.BiometricsCephalon, Inc.FrazerUSA

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