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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of oral tiopronin (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 79-84 
    Details
    ISSN: 1432-1041
    Keywords: Tiopronin ; 2-Mercaptopropionylglycine ; bioavailability ; urinary excretion ; cystine urolithiasis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten healthy subjects were given 500 mg (3064 μmol) tiopronin, or 2-mercaptopropionylglycine (2-MPG) by mouth. Cmax was reached after 3–6 h, and after a shorter β-phase a long terminal half-life of 53 h of total tiopronin was found. Tiopronin measured as unbound (non-protein-bound) drug disappeared more rapidly from plasma, with a calculated t 1/2 of 1.8 h. Mean residence time was higher (58 h) when calculated as total tiopronin than as unbound tiopronin (6 h), and this was also the case for the volume of distribution (Vλ=4551 vs Vλ,u=41 1). The results indicate extensive protein binding in plasma and a deep pool of tissue bound tiopronin after the first absorption and distribution phases. Absolute bioavailability (f) was 63%, and bioavailability calculated from urinary excretion was 47%, which are well correlated with each other. Urinary excretion was mainly confined to the first 6 h (74%) and was almost complete (98%) within 12 h. We conclude that the maximal absorption of the tiopronin was late, protein and tissue binding of the drug were high and its bioavailability varied. The renal excretion of low molecular weight tiopronin occurred early, which implies that the drug should be given in divided doses, at least twice daily, for optimal efficiency in the treatment of cystinuria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315354
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  • 2
    Electronic Resource
    Electronic Resource
    Determinations of 5-hydroxyindoleacetic acid and homovanillic acid in human CSF with monitoring of probenecid levels in CSF and plasma (1987)
    Springer
    Psychopharmacology 92 (1987), S. 144-149 
    Details
    ISSN: 1432-2072
    Keywords: Probenecid ; 5-HIAA ; HVA ; Plasma levels ; CSF ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The accumulation of 5-HIAA and HVA in cerebrospinal fluid (CSF) was studied in eight healthy volunteers after oral administration of probenecid. Simulation indicated that a dose of 4.5 g probenecid should be used to achieve probenecid plasma concentrations between 200 and 400 μg/ml. Almost complete inhibition of the active transport of the acidic metabolites was assumed to be obtained at these concentrations. Probenecid 4.5 g was administered in two doses (2.5 g and 2 g), separated by 4 h. Plasma samples were drawn at varying intervals over a period of 46 h and lumbar puncture (LP) was performed at either 14 h or 20 h after the first administration of probenecid. The concentration of probenecid, 5-HIAA and HVA in CSF was estimated and the probenecid-induced accumulation of 5-HIAA and HVA was compared with their baseline values. There were no statistically significant differences (P〉0.05) in the accumulation of the monoamine metabolites between the two LP (14 h and 20 h), neither were there any differences in CSF concentrations of probenecid at the time of LP. There were only small differences in probenecid plasma concentrations, although statistically significant. Due to maximum blockade of the active transport system no correlation was observed between the CSF concentration of probenecid and the induced accumulation of 5-HIAA and HVA, respectively. The range of probenecid-induced accumulation for 5-HIAA and HVA in these volunteers was 156–429% and 183–600%, respectively. The suggested monitoring of probenecid plasma levels is proposed as a suitable model to investigate central neuronal activity of dopamine and serotonin in the central nervous system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177906
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    Paper (German National Licenses)
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