Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion
Article first published online: 16 AUG 2006
British Journal of Clinical Pharmacology
Volume 63, Issue 1, pages 36–40, January 2007
How to Cite
Fidler, M. C., Barshop, B. A., Gangoiti, J. A., Deutsch, R., Martin, M., Schneider, J. A. and Dohil, R. (2007), Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion. British Journal of Clinical Pharmacology, 63: 36–40. doi: 10.1111/j.1365-2125.2006.02734.x
- Issue published online: 16 AUG 2006
- Article first published online: 16 AUG 2006
- Received 27 January 2006Accepted 12 April 2006Published OnlineEarly16 August 2006
- plasma cysteamine;
- tandem mass spectrometry
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.
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.
The rate and extent of drug absorption were assessed by comparing AUC(0, ∞), Cmax and tmax, among the gastrointestinal infusion sites. Total cysteamine exposure, expressed as area under the curve (AUC(0, ∞)) was greatest when the drug was infused into the small intestine (4331.3 ± 1907.6 min × µm) followed by stomach (3901.9 ± 1591.9 min × µm) and caecum (3141.4 ± 1627.6 min × µm). Cysteamine infusion into the small intestine resulted in the most rapid rise to maximal plasma concentrations (tmax = 21 ± 0.56 min); tmax was delayed to 50 ± 26 min and 64 ± 26 min after gastric and caecal infusion, respectively. The maximum cysteamine plasma concentration (Cmax) was reached after infusion of the drug into the small intestine (51 ± 21 µm), which was higher than plasma Cmax concentrations after gastric (39 ± 16 µm) and caecal infusion (23 ± 15 µm).
The pharmacokinetic data generated help extend our understanding of cysteamine.