Sodium thiosulfate pharmacokinetics in hemodialysis patients and healthy volunteers.
Clin J Am Soc Nephrol
; 6(6): 1447-55, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21566113
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 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiossulfatos
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Fármacos Cardiovasculares
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Diálise Renal
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Nefropatias
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Clin J Am Soc Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Suíça