succimer has been researched along with Cystinuria* in 2 studies
2 other study(ies) available for succimer and Cystinuria
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Studies of urinary cystine precipitation in vitro: ontogeny of cystine nephrolithiasis and identification of meso-2,3-dimercaptosuccinic acid as a potential therapy for cystinuria.
Children with fully recessive (Type I/I) cystinuria have a high risk of stone formation in the first decade of life. To assess the tendency for cystine to precipitate in individual urine samples, we developed an in vitro assay in which radiolabelled cystine (4mM) was dissolved in urine at 37 degrees C after alkalization to pH 10. Samples were then brought to pH 5, cooled, and centrifuged. The % decrease in supernatant cpm was used as a measure of cystine precipitation (CP). CP varied widely among normal children (74%+/-34) whereas variability of repeated determinations on a single adult individual was modest (64%+/-3.3). The assay was used to compare various potential therapies for cystinuria. Precipitation of exogenous cystine from normal urine was strongly inhibited by addition of D-penicillamine (CP: 8%+/-3) or dimercaptosuccinic acid (DMSA) (CP: 5%+/-1), at urinary concentrations attained by standard oral doses of each drug. Mercaptopropionylglycine (MPG) was moderately effective (CP: 43%+/-9), whereas captopril was a weak inhibitor (CP: 63%+/-12). Precipitation of endogenous cystine (2191 micromol/L) from a cystinuric patient showed that DMSA and D-penicillamine were again highly effective compared to the other agents. In addition DMSA and penicillamine added to the same patient's urine reduced the free cystine by 50% (as measured by automated amino acid analyzer) whereas MPG and captopril had no effect. In conclusion, DMSA is comparable to D-penicillamine as an in vitro inhibitor. Topics: Adolescent; Age Factors; Chemical Precipitation; Child; Child, Preschool; Cystine; Cystinuria; Dose-Response Relationship, Drug; Humans; Infant; Kidney Diseases; Lithiasis; Penicillamine; Reference Values; Succimer; Tiopronin; Urine | 2003 |
Determination and metabolism of dithiol chelating agents. VI. Isolation and identification of the mixed disulfides of meso-2,3-dimercaptosuccinic acid with L-cysteine in human urine.
Virtually nothing is known about the biotransformation of the heavy metal chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA). Two fasted, normal, young men were given 10.0 mg DMSA/kg po, and their urines were collected over a 14-hr period. Urine samples were analyzed, before and after electrolytic reductive treatment, for DMSA and its biotransformants using bromobimane derivatization, HPLC separation, and fluorescence detection. Metabolites were isolated by HPLC, ion-pairing extraction, ion-exchange extraction, and TLC. By 14 hr after DMSA administration, 87% of the total DMSA and 95% of the total L-cysteine found in urine consisted of altered forms of these compounds. The urinary excretion of altered DMSA, at 1, 2, 4, 6, 9, and 14 hr after administration of DMSA, when compared to the urinary excretion of altered L-cysteine had a correlation coefficient of 0.952 and p less than 0.003. Approximately 90% of the altered DMSA excreted in the 2- to 4-hr urine was found in disulfide linkage with L-cysteine. The remaining 10% was found as cyclic disulfides of DMSA. Of the mixed disulfides found in 4- to 6-hr urine, 97% consisted of two L-cysteine residues per one DMSA and the remaining 3% consisted of one L-cysteine per one DMSA. The 2:1 mixed disulfides (97%) were isolated as three distinct species by TLC, consisting of 77, 12, and 8% of the total mixed disulfides found. In addition to the novelty of these biotransformants of DMSA, the DMSA-cysteine mixed disulfides indicate a thiol-disulfide interchange between DMSA and L-cystine. The discovery of the formation of these water soluble DMSA-cysteine mixed disulfides should encourage the evaluation of DMSA in the treatment of cystinuria. Topics: Adult; Biotransformation; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Copper; Cysteine; Cystinuria; Disulfides; Humans; Lead; Male; Species Specificity; Succimer; Sulfhydryl Compounds; Zinc | 1989 |