Dose comparison of conivaptan (Vaprisol®) in patients with euvolemic or hypervolemic hyponatremia – efficacy, safety, and pharmacokinetics

Biff F. Palmer, Amy D. Rock, Emily J. Woodward

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Purpose: This study aimed to evaluate the efficacy, safety, and pharmacokinetics of 20 and 40 mg/day conivaptan (Vaprisol®) in patients with hypervolemic or euvolemic hyponatremia. Methods: Hyponatremic patients – serum sodium (sNa) ≤130 mEq/L – received either 20 or 40 mg/day of conivaptan for 4 days, following an initial 20 mg loading dose. Efficacy was evaluated by the magnitude and extent of change in sNa. Safety was evaluated by the incidence of adverse events, changes in vital signs and laboratory parameters, rate of sNa correction, and frequency of infusion-site reactions. Pharmacokinetic parameters were also measured. Results: A total of 37 patients received 20 mg/day and 214 patients received 40 mg/day conivaptan. Baseline-adjusted sNa-area under the concentration–time curve increased by an average of 753.8±499.9 mEq⋅hr/L (20 mg/day) and 689.2±417.3 mEq⋅hr/L (40 mg/day) over the course of the 4-day treatment period. The majority of patients in both treatment groups achieved a 4 mEq/L increase in sNa over baseline in ~24 hours (82.5%). Average increase in sNa after 4 days was ~10 mEq/L, varying with dosage level and baseline volume status. Treatment success (normal sNa or increase of ≥6 mEq/L) was attained by 70.3% of patients in the 20 mg/day group and 72.0% in the 40 mg/day group. Conclusion: Both 20 and 40 mg/day doses of conivaptan are efficacious in increasing sNa over 4 days of treatment with no observed increase in the frequency of adverse events or specific infusion-site reactions using the higher dose. The pharmacokinetic parameters of both doses were similar to what has been reported previously, exhibiting greater-than-dose-proportional plasma concentrations.

Original languageEnglish (US)
Pages (from-to)339-351
Number of pages13
JournalDrug Design, Development and Therapy
StatePublished - Jan 18 2016


  • Critical care
  • Electrolyte
  • Osmotic demyelination syndrome
  • Thiazide
  • V receptor antagonist

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery


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