Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion.
OBJECTIVE
Although cysteamine was first used in the treatment of cystinosis in 1976 and approved by the FDA as cysteamine bitartrate (Cystagon) in 1994, surprisingly little pharmacological data are available for this compound. Cysteamine and its related drugs are currently being evaluated for the treatment of Huntington's and Parkinson's disease. The aim of te study was to understand the pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion.


METHODS
Cysteamine bitartrate was delivered through a naso-enteric catheter into the stomach (n = 8), small intestine (n = 8) and caecum (n = 4) of normal subjects. Plasma cysteamine concentrations were determined using LC-MS/MS.


RESULTS
The rate and extent of drug absorption were assessed by comparing AUC(0, infinity), C(max) and t(max), among the gastrointestinal infusion sites. Total cysteamine exposure, expressed as area under the curve (AUC(0, infinity)) was greatest when the drug was infused into the small intestine (4331.3 +/- 1907.6 min x microM) followed by stomach (3901.9 +/- 1591.9 min x microM) and caecum (3141.4 +/- 1627.6 min x microM). Cysteamine infusion into the small intestine resulted in the most rapid rise to maximal plasma concentrations (t(max) = 21 +/- 0.56 min); t(max) was delayed to 50 +/- 26 min and 64 +/- 26 min after gastric and caecal infusion, respectively. The maximum cysteamine plasma concentration (C(max)) was reached after infusion of the drug into the small intestine (51 +/- 21 microM), which was higher than plasma C(max) concentrations after gastric (39 +/- 16 microM) and caecal infusion (23 +/- 15 microM).


CONCLUSIONS
The pharmacokinetic data generated help extend our understanding of cysteamine.
Fidler
Meredith C
MC
Department of Paediatrics and Family, University of California at San Diego, La Jolla, California, USA.
Barshop
Bruce A
BA
Gangoiti
Jon A
JA
Deutsch
Reena
R
Martin
Michael
M
Schneider
Jerry A
JA
Dohil
Ranjan
R
D000328:Adult; D019540:Area Under Curve; D003543:Cysteamine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003554:Cystinosis / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011446:Prospective Studies
D018697:Nootropic Agents; D003543:Cysteamine