title: Sodium thiosulfate pharmacokinetics in hemodialysis patients and healthy volunteers.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  STS was given intravenously to 10 hemodialysis patients on- and 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.
authors.affiliation: Department of Nephrology and Hypertension, Inselspital, University of Bern, Bern, Switzerland. stefan.farese@insel.ch
authors.forename: Stefan
authors.initials: S
authors.lastname: Farese
authors.forename: Emilie
authors.initials: E
authors.lastname: Stauffer
authors.forename: Robert
authors.initials: R
authors.lastname: Kalicki
authors.forename: Tatjana
authors.initials: T
authors.lastname: Hildebrandt
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Frey
authors.forename: Felix J
authors.initials: FJ
authors.lastname: Frey
authors.forename: Dominik E
authors.initials: DE
authors.lastname: Uehlinger
authors.forename: Andreas
authors.initials: A
authors.lastname: Pasch
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001682:Biological Availability; D001711:Biotransformation; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D006435:Renal Dialysis; D013557:Switzerland; D013885:Thiosulfates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D002317:Cardiovascular Agents; D013885:Thiosulfates; C017717:sodium thiosulfate