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Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias.

Publication ,  Journal Article
Shoaf, SE; Elizari, MV; Wang, Z; Sekar, K; Grinfeld, LR; Barbagelata, NA; Lerman, J; Bramer, SL; Trongé, J; Orlandi, C
Published in: J Cardiovasc Pharmacol Ther
September 2005

BACKGROUND: Tolvaptan, a nonpeptide selective vasopressin receptor (V2) antagonist, is in development for the treatment of congestive heart failure and hyponatremia. Tolvaptan is primarily metabolized via CYP3A4. This study was conducted to determine the extent of the pharmacokinetic interaction between tolvaptan and steady state amiodarone, an antiarrhythmic drug commonly prescribed for patients with congestive heart failure and a known inhibitor of other drugs metabolized by CYP3A4. METHODS: This was a multicenter, open-label, 1-arm, 3-period, sequential treatment study conducted in 11 men (10) and women aged 49 to 80 years. They were primarily Caucasian (20) subjects, with a history of cardiac arrhythmias who were otherwise healthy. Subjects were to have been on oral amiodarone maintenance therapy of 200 mg/day for at least 10 months. All subjects took 200 mg amiodarone once daily on each study day; on days 3 and 4, they were also coadministered 30 and 90 mg of tolvaptan, respectively. The plasma concentrations of amiodarone and its metabolite desethylamiodarone were determined for 24 hours postdose on days 2, 3, and 4, tolvaptan concentrations were determined for 24 hours postdose on days 3 and 4. RESULTS: As determined by the ratio of the geometric means and 90% confidence intervals (0.5 to 2.0) for the maximal plasma concentration and the area under the curve during the dosing interval for both amiodarone and desethylamiodarone, tolvaptan coadministration had no effect on either amiodarone and desethylamiodarone disposition, as all the geometric mean ratios (amiodarone + tolvaptan [30 or 90 mg] vs amiodarone alone) were approximately 1. CONCLUSION: Tolvaptan coadministration does not alter steady-state amiodarone or desethylamiodarone concentrations. Tolvaptan concentrations did not appear to be different from historical controls. The most frequently reported adverse event was polyuria (15 of 21 subjects for amiodarone + 30 mg tolvaptan); an expected outcome due to the known potent aquaretic action of tolvaptan. The combination of amiodarone and tolvaptan was well tolerated.

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Published In

J Cardiovasc Pharmacol Ther

DOI

ISSN

1074-2484

Publication Date

September 2005

Volume

10

Issue

3

Start / End Page

165 / 171

Location

United States

Related Subject Headings

  • Tolvaptan
  • Middle Aged
  • Male
  • Humans
  • Female
  • Electrocardiography
  • Drug Interactions
  • Cardiovascular System & Hematology
  • Benzazepines
  • Arrhythmias, Cardiac
 

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Shoaf, S. E., Elizari, M. V., Wang, Z., Sekar, K., Grinfeld, L. R., Barbagelata, N. A., … Orlandi, C. (2005). Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias. J Cardiovasc Pharmacol Ther, 10(3), 165–171. https://doi.org/10.1177/107424840501000304
Shoaf, Susan Elizabeth, Marcelo Víctor Elizari, Zhao Wang, Kumara Sekar, Liliana Rosa Grinfeld, N Alejandro Barbagelata, Jorge Lerman, Steven Lee Bramer, Jorge Trongé, and Cesare Orlandi. “Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias.J Cardiovasc Pharmacol Ther 10, no. 3 (September 2005): 165–71. https://doi.org/10.1177/107424840501000304.
Shoaf SE, Elizari MV, Wang Z, Sekar K, Grinfeld LR, Barbagelata NA, et al. Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias. J Cardiovasc Pharmacol Ther. 2005 Sep;10(3):165–71.
Shoaf, Susan Elizabeth, et al. “Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias.J Cardiovasc Pharmacol Ther, vol. 10, no. 3, Sept. 2005, pp. 165–71. Pubmed, doi:10.1177/107424840501000304.
Shoaf SE, Elizari MV, Wang Z, Sekar K, Grinfeld LR, Barbagelata NA, Lerman J, Bramer SL, Trongé J, Orlandi C. Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias. J Cardiovasc Pharmacol Ther. 2005 Sep;10(3):165–171.
Journal cover image

Published In

J Cardiovasc Pharmacol Ther

DOI

ISSN

1074-2484

Publication Date

September 2005

Volume

10

Issue

3

Start / End Page

165 / 171

Location

United States

Related Subject Headings

  • Tolvaptan
  • Middle Aged
  • Male
  • Humans
  • Female
  • Electrocardiography
  • Drug Interactions
  • Cardiovascular System & Hematology
  • Benzazepines
  • Arrhythmias, Cardiac