Advances in Therapy

, Volume 26, Issue 2, pp 230–240 | Cite as

Pharmacokinetics of digoxin in healthy subjects receiving taranabant, a novel cannabinoid-1 receptor inverse agonist

  • Andrew E. Denker
  • Gaetano Morelli
  • Laura K. Vessey
  • Susie Li
  • Jinyu Yuan
  • Stephanie Dunbar
  • Nicole M. Lewis
  • William Taggart
  • John A. Wagner
Original Research
First Online:
Received:

Abstract

Introduction

Interaction studies with digoxin (Lanoxin®; GlaxoSmithKline, Research Triangle Park, NC, USA), a commonly prescribed cardiac glycoside with a narrow therapeutic index and a long half-life, are typically required during the development of a new drug, particularly when it is likely that digoxin may be given to patients also treated with the new agent, taranabant—a cannabinoid-1 receptor inverse agonist—for weight loss. This study was designed to establish if this combination of therapy has the potential of a significant pharmacokinetic interaction.

Methods

This open-label, fixed-sequence, two-period study investigated whether taranabant, administered to steady state, affects the well-described single-dose pharmacokinetics of digoxin. During the first period, 12 healthy men and women ranging in age from 21 to 35 years received a single oral dose of digoxin 0.5 mg. Following a 10-day wash out, they started a 19-day taranabant dosing regimen (6 mg once daily from day −14 to day 5) designed to establish and maintain steady-state levels of taranabant. On study day 1, subjects received a single oral dose of digoxin 0.5 mg. The plasma levels of digoxin were followed for an additional 4 days while the dosing of taranabant continued.

Results

The geometric mean ratio and 90% confidence intervals for digoxin AUC0-∞ were 0.91 (0.83, 0.99), falling within the prespecified comparability intervals (CI) of (0.8, 1.25), which is within the usually allowed interval for bioequivalence. The geometric mean ratio and 90% CI for digoxin maximum plasma concentration (Cmax) were 1.23 (1.09, 1.40). The median time to Cmax was the same for both treatments.

Conclusion

Multiple doses of 6 mg taranabant do not have a clinically meaningful effect on the pharmacokinetics of a single oral dose of digoxin.

Keywords

cannabinoid-1 receptor inverse agonist CB1R digoxin taranabant pharmacokinetics 
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Copyright information

© Springer Healthcare Communications 2009

Authors and Affiliations

  • Andrew E. Denker
    • 1
  • Gaetano Morelli
    • 2
  • Laura K. Vessey
    • 3
    • 4
  • Susie Li
    • 5
  • Jinyu Yuan
    • 3
    • 4
    • 6
  • Stephanie Dunbar
    • 3
    • 4
    • 7
  • Nicole M. Lewis
    • 3
    • 4
  • William Taggart
    • 3
    • 4
  • John A. Wagner
    • 3
    • 4
  1. 1.Merck Research Laboratories BostonBostonUSA
  2. 2.MDS Pharma ServicesSaint Laurent, MontrealCanada
  3. 3.Merck Research LaboratoriesUpper GwyneddUSA
  4. 4.Merck Research LaboratoriesRahwayUSA
  5. 5.Merck Research LaboratoriesWest PointUSA
  6. 6.Pfizer Inc.New YorkUSA
  7. 7.Teva LLCHorshamUSA

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