title: A comparison of the effectiveness of cysteamine and phosphocysteamine in elevating plasma cysteamine concentration and decreasing leukocyte free cystine in nephropathic cystinosis.
abstract: Cysteamine (beta-mercaptoethylamine, MEA) is currently used to treat children with nephropathic cystinosis. In this study MEA was compared to phosphocysteamine (MEAP), a phosphorothioester that tastes and smells better than MEA, with respect to its ability to elevate plasma MEA and deplete leukocytes of cystine. Studies were performed in six children with nephropathic cystinosis ranging in age from 2 to 10 yr. After equimolar oral doses of either MEA or MEAP plasma cysteamine was determined at various times for 6 h. MEA was determined by sodium borohydride reduction followed by high-performance liquid chromatography separation and electrochemical detection. Leukocyte cystine was measured before and 1 and 6 h after drug administration. Peak plasma MEA was obtained 30 min to 1 h after a dose and was not significantly different when MEA (48.6 +/- 10.7, mean +/- SD) or MEAP (54.1 +/- 20.2) was given. Significant plasma MEA concentrations were seen as early as 15 min after an oral dose, indicating rapid absorption. Analysis of vomitus indicated that hydrolysis of the phosphate group of MEAP occurs in the stomach. The percent decrease in leukocyte cystine content obtained with MEA administration (61.9%) was not significantly different from the decrease observed when MEAP was administered (65.3%). MEA and MEAP appear to be equally effective in their cystine-depleting properties.
authors.affiliation: Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla 92093.
authors.forename: L A
authors.initials: LA
authors.lastname: Smolin
authors.forename: K F
authors.initials: KF
authors.lastname: Clark
authors.forename: J G
authors.initials: JG
authors.lastname: Thoene
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
authors.forename: J A
authors.initials: JA
authors.lastname: Schneider
mesh_terms: D000284:Administration, Oral; D002648:Child; D002675:Child, Preschool; D003539:Cystaphos / Q000009:adverse effects / Q000627:therapeutic use*; D003543:Cysteamine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003553:Cystine / Q000097:blood*; D003554:Cystinosis / Q000097:blood / Q000188:drug therapy*; D005766:Gastrointestinal Contents / Q000032:analysis; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000032:analysis; D009946:Organothiophosphorus Compounds / Q000627:therapeutic use*; D010342:Patient Acceptance of Health Care; D014839:Vomiting / Q000139:chemically induced
chemical_list: D009946:Organothiophosphorus Compounds; D003553:Cystine; D003543:Cysteamine; D003539:Cystaphos