Sodium thiosulfate pharmacokinetics in hemodialysis patients and healthy volunteers

authored by

Stefan Farese, Emilie Stauffer, Robert Kalicki, Tatjana Hildebrandt, Brigitte M. Frey, Felix J. Frey, Dominik E. Uehlinger, Andreas Pasch

Abstract

Background and objectives Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet. Design, setting, participants, & measurements STS was given intravenously to 10 hemodialysis patients onand off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method. Results In volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5±1.82 versus 7.1±2.7 μmol/L. Renal clearance was high in volunteers (1.86±0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25±0.32 ml/min per kg) than in anuric patients (2.04±0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62±1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%). Conclusions Given the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS

Organisation(s)

Institute of Plant Genetics

External Organisation(s)

University of Bern

Type

Article

Journal

Clinical Journal of the American Society of Nephrology

Volume

6

Pages

1447-1455

No. of pages

9

ISSN

1555-9041

Publication date

01.06.2011

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Epidemiology, Critical Care and Intensive Care Medicine, Nephrology, Transplantation

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.2215/CJN.10241110 (Access: Open)