TY - JOUR

T1 - Sodium thiosulfate pharmacokinetics in hemodialysis patients and healthy volunteers

AU - Farese, Stefan

AU - Stauffer, Emilie

AU - Kalicki, Robert

AU - Hildebrandt, Tatjana

AU - Frey, Brigitte M.

AU - Frey, Felix J.

AU - Uehlinger, Dominik E.

AU - Pasch, Andreas

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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

AB - 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

UR - http://www.scopus.com/inward/record.url?scp=79958194869&partnerID=8YFLogxK

U2 - 10.2215/CJN.10241110

DO - 10.2215/CJN.10241110

M3 - Article

C2 - 21566113

AN - SCOPUS:79958194869

VL - 6

SP - 1447

EP - 1455

JO - Clinical Journal of the American Society of Nephrology

JF - Clinical Journal of the American Society of Nephrology

SN - 1555-9041

IS - 6

ER -