Pharmacokinetics of enteric-coated cysteamine bitartrate in healthy adults: a pilot study

Authors


Dr Ranjan Dohil, UCSD Medical Center, Hillcrest, 200 West Arbor Dr, San Diego, CA 92103-8450, USA.
Tel.: + 1 619 543 2049
Fax: + 1 619 543 7537
E-mail: rdohil@ucsd.edu

Abstract

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 Cmax 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 tmax 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 Cmax 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 tmax following cysteamine bitartrate enteric-coated suggested that the cysteamine was released enterically.

Ancillary