Twice-daily cysteamine bitartrate therapy for children with cystinosis.
OBJECTIVE
Cystinosis causes renal and other organ failure. Regular 6-hourly cysteamine bitartrate (Cystagon; Mylan, Morgantown, West Virginia) reduces intracellular cystine and the rate of organ deterioration. A formulation of cysteamine requiring less frequent dosing may improve compliance and possibly patient outcome.


METHODS
Enteric-release cysteamine was prepared. For a period of 1 month, patients received their regular cysteamine dose every 6 hours (stage I). The patients then underwent pharmacokinetic and pharmacodynamic studies following washout periods using single-doses of cysteamine and enteric-release cysteamine (stage II). Finally, the patients commenced regular enteric-release cysteamine therapy (stage III). Weekly trough white blood cell (WBC) cystine levels were recorded.


RESULTS
Seven children with cystinosis (mean age, 11.8 years; range, 8-17 years) who received cysteamine and enteric-release cysteamine (mean dose, 45 and 28.8 mg/kg body weight/day, respectively) had mean WBC cystine levels of 0.7+/-0.3 and 0.41+/-0.22 nmol half-cystine/mg protein in study stages I and III, respectively. Study stage II showed that the mean time (T(max)) to reach the maximum plasma cysteamine level (C(max)) was longer for enteric-release cysteamine than for cysteamine (176 minutes vs 60 minutes; P=.001), but the mean C(max) at the same dose was similar. Mean serum gastrin levels were similar after ingestion of cysteamine and enteric-release cysteamine.


CONCLUSIONS
Twelve-hour enteric-release cysteamine, given at approximately 60% of the previous daily dose of cysteamine, was effective in maintaining trough WBC cystine levels within a satisfactory range.
Department of Pediatrics, University of California San Diego, La Jolla, CA 92103-8450, USA. rdohil@ucsd.edu
Ranjan
R
Dohil
Meredith
M
Fidler
Jon A
JA
Gangoiti
Frederick
F
Kaskel
Jerry A
JA
Schneider
Bruce A
BA
Barshop
D000293:Adolescent; D002648:Child; D003543:Cysteamine / Q000008:administration & dosage* / Q000097:blood; D003554:Cystinosis / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D005260:Female; D005755:Gastrins / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D011837:Radiation-Protective Agents / Q000008:administration & dosage*
D003692:Delayed-Action Preparations; D005755:Gastrins; D011837:Radiation-Protective Agents; D003543:Cysteamine