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Low-dose tolvaptan PK/PD: comparison of patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion to healthy adults

PURPOSE: Tolvaptan (TLV) is indicated to treat hyponatremia due to syndrome of inappropriate diuretic hormone (SIADH) in Europe. Treatment is to be initiated at 15 mg QD but post-approval reporting indicates increasing use of 7.5 mg as the starting dose. Physicians believe 7.5 mg is effective and ha...

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Autores principales: Shoaf, Susan E., Bricmont, Patricia, Dandurand, Ann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662662/
https://www.ncbi.nlm.nih.gov/pubmed/28803333
http://dx.doi.org/10.1007/s00228-017-2302-7
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author Shoaf, Susan E.
Bricmont, Patricia
Dandurand, Ann
author_facet Shoaf, Susan E.
Bricmont, Patricia
Dandurand, Ann
author_sort Shoaf, Susan E.
collection PubMed
description PURPOSE: Tolvaptan (TLV) is indicated to treat hyponatremia due to syndrome of inappropriate diuretic hormone (SIADH) in Europe. Treatment is to be initiated at 15 mg QD but post-approval reporting indicates increasing use of 7.5 mg as the starting dose. Physicians believe 7.5 mg is effective and has a lower incidence of overly rapid correction of serum sodium. METHODS: Single TLV doses of 3.75, 7.5, and 15 mg were administered to 14 healthy adults in a crossover design and to 29 subjects ≥18 years with SIADH and serum sodium between 120 and 133 mmol/L in a parallel-group design. Pharmacodynamics and TLV plasma concentrations were assessed for 24 h post-dose. RESULTS: In SIADH subjects, corrections of serum sodium (Δ of ≥8 mmol/L in the first 8 h or ≥12 mmol/L in the first 24 h) were observed in one, one, and two subjects in the 3.75-, 7.5-, and 15-mg dose groups. Fluid balance (FB) for 0–6 h post-dose was correlated (r (2) = 0.37) with maximum increases in serum sodium; subjects with large corrections had large (~1 L) negative FB. Compared to healthy adults, subjects with SIADH did not drink in response to their negative FB and had larger increases in serum sodium at 24 h. Median time of maximum increase in healthy adults was 6 h, with no rapid corrections, and FB was near 0 mL by 24 h. CONCLUSION: Starting titration with 7.5 mg TLV will not eliminate the risk of rapid corrections in serum sodium. Monitoring FB may indicate that a subject is at risk for over correction.
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spelling pubmed-56626622017-11-15 Low-dose tolvaptan PK/PD: comparison of patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion to healthy adults Shoaf, Susan E. Bricmont, Patricia Dandurand, Ann Eur J Clin Pharmacol Pharmacodynamics PURPOSE: Tolvaptan (TLV) is indicated to treat hyponatremia due to syndrome of inappropriate diuretic hormone (SIADH) in Europe. Treatment is to be initiated at 15 mg QD but post-approval reporting indicates increasing use of 7.5 mg as the starting dose. Physicians believe 7.5 mg is effective and has a lower incidence of overly rapid correction of serum sodium. METHODS: Single TLV doses of 3.75, 7.5, and 15 mg were administered to 14 healthy adults in a crossover design and to 29 subjects ≥18 years with SIADH and serum sodium between 120 and 133 mmol/L in a parallel-group design. Pharmacodynamics and TLV plasma concentrations were assessed for 24 h post-dose. RESULTS: In SIADH subjects, corrections of serum sodium (Δ of ≥8 mmol/L in the first 8 h or ≥12 mmol/L in the first 24 h) were observed in one, one, and two subjects in the 3.75-, 7.5-, and 15-mg dose groups. Fluid balance (FB) for 0–6 h post-dose was correlated (r (2) = 0.37) with maximum increases in serum sodium; subjects with large corrections had large (~1 L) negative FB. Compared to healthy adults, subjects with SIADH did not drink in response to their negative FB and had larger increases in serum sodium at 24 h. Median time of maximum increase in healthy adults was 6 h, with no rapid corrections, and FB was near 0 mL by 24 h. CONCLUSION: Starting titration with 7.5 mg TLV will not eliminate the risk of rapid corrections in serum sodium. Monitoring FB may indicate that a subject is at risk for over correction. Springer Berlin Heidelberg 2017-08-12 2017 /pmc/articles/PMC5662662/ /pubmed/28803333 http://dx.doi.org/10.1007/s00228-017-2302-7 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Pharmacodynamics
Shoaf, Susan E.
Bricmont, Patricia
Dandurand, Ann
Low-dose tolvaptan PK/PD: comparison of patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion to healthy adults
title Low-dose tolvaptan PK/PD: comparison of patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion to healthy adults
title_full Low-dose tolvaptan PK/PD: comparison of patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion to healthy adults
title_fullStr Low-dose tolvaptan PK/PD: comparison of patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion to healthy adults
title_full_unstemmed Low-dose tolvaptan PK/PD: comparison of patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion to healthy adults
title_short Low-dose tolvaptan PK/PD: comparison of patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion to healthy adults
title_sort low-dose tolvaptan pk/pd: comparison of patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion to healthy adults
topic Pharmacodynamics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662662/
https://www.ncbi.nlm.nih.gov/pubmed/28803333
http://dx.doi.org/10.1007/s00228-017-2302-7
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