Pharmacokinetics of cysteamine in a cystinosis patient treated with hemodialysis

Abstract

Sirs, Cystinosis is a rare autosomal recessive disease caused by mutations in the CTNS gene, resulting in lysosomal accumulation of the amino acid cystine in cells throughout the body. Most patients develop general proximal tubular damage, called renal Fanconi syndrome, within the first year of life. Besides kidney involvement, the disease can manifest in the eyes, various endocrine organs, central nervous system, and muscles. If not treated with the cystine-depleting agent cysteamine, patients will develop end-stage renal disease (ESRD) around the age of 10 years. The advised dose of cysteamine is 1.30 g/m 2 body surface area, with a maximum of 1.95 g/m 2 , divided into four equal doses. Recently, questions have been raised whether or not to decrease cysteamine dose in cystinosis patients with ESRD, as clearance of the drug might be lowered. We present a pharmacokinetic study of cysteamine in a cystinosis patient with ESRD treated with hemodialysis. The patient is a 19-year-old man. The diagnosis of cystinosis was made at the age of 1 year and confirmed by mutation analysis of the CTNS gene, revealing a homozygous c.926 duplication. At the time of this study, he had been on hemodialysis since 1 year after failure of his second kidney graft. Cysteamine plasma levels were measured before and every 60 min after ingestion of 15 mg/kg cysteamine for a total duration of 6 hours. This study of cysteamine pharmacokinetics was conducted in fouradditionalcystinosispatients(agerange12–29years), all of whom had a functioning renal graft [glomerular filtration rate (GFR) 72–109 mL/min/1.73 m 2 ]. The results are shown in Fig. 1. A reduced GFR did not lead to increased plasma levels of cysteamine. Conversely, the patient on hemodialysis had the lowest area under the curve (AUC) compared with the patients with a functioning renal graft (46 vs. 58–136 μmol/l, respectively).