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Pharmacokinetics of enteric‐coated cysteamine bitartrate in healthy adults: a pilot study
Author(s) -
Gangoiti Jon A.,
Fidler Meredith,
Cabrera Betty L.,
Schneider Jerry A.,
Barshop Bruce A.,
Dohil Ranjan
Publication year - 2010
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2010.03721.x
Subject(s) - cysteamine , pharmacokinetics , cystinosis , medicine , enteric coating , ingestion , gastroenterology , pharmacology , endocrinology , chemistry , dosage form , biochemistry , cystine , cysteine , enzyme
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Cysteamine bitartrate is taken lifelong, every 6 h and for the treatment of cystinosis. Recent studies using cysteamine for for other diseases such as neurodegenerative disorders adopt the same dosing regimen for cysteamine. Regular cysteamine bitartrate (Cystagon) may cause upper gastrointestinal symptoms in some patients. WHAT THIS STUDY ADDS • This is the only study that provides pharmacokinetic data for cysteamine delivered in an enteric‐release preparation in normal subjects. EC‐cysteamine is very well tolerated and does not cause increased gastrin concentrations, even at relatively high doses. • EC‐cysteamine at the higher dose results in better drug uptake as measured by C max and AUC and is more likely to be effective. AIMS Cysteamine bitartrate (Cystagon®) is the approved treatment for cystinosis. Poor compliance and patient outcome may occur because the drug needs to be taken every 6 h and in some patients causes gastrointestinal symptoms due to hypergastrinaemia. A formulation of cysteamine requiring twice daily ingestion would improve the quality of life for these patients. This study compares the pharmacokinetics and gastrin production following cysteamine bitartrate non‐enteric‐coated and cysteamine bitartrate enteric‐coated in normal healthy subjects. METHODS Enteric‐coated cysteamine was prepared. Following single doses of cysteamine bitartrate non‐enteric‐coated 450 mg and cysteamine bitartrate enteric‐coated 450 mg and 900 mg, serial plasma cysteamine and gastrin concentrations were measured. Two subjects also received cysteamine bitartrate non‐enteric‐coated 900 mg. Gastrointestinal (GI) symptoms were recorded. RESULTS Six healthy adults (mean age 20.7 years, range 18–24 years; mean weight 59.3 kg) received drug. All post‐dose gastrin concentrations were within the normal range (<100 pg ml –1 ). The t max following cysteamine bitartrate non‐enteric‐coated (mean and SD is 75 ± 19 min) was shorter than cysteamine bitartrate enteric‐coated (220 ± 74 min) ( P = 0.001), but only the C max and AUC estimates following 900 mg cysteamine bitartrate enteric‐coated were significantly greater than any of the other preparations or doses ( P < 0.05). One patient had GI symptoms following both 900 mg cysteamine bitartrate non‐enteric‐coated and cysteamine bitartrate enteric‐coated. CONCLUSION Although patient numbers were low, single high doses of cysteamine bitartrate enteric‐coated were better tolerated than similar doses of cysteamine bitartrate non‐enteric‐coated in the healthy subjects and all had normal gastrin concentrations. The delayed t max following cysteamine bitartrate enteric‐coated suggested that the cysteamine was released enterically.