Enteric-Coated Cysteamine Bitartrate in Cystinosis Patients

被引:2
作者
Klank, Sabrina [1 ]
van Stein, Christina [1 ]
Grueneberg, Marianne [1 ]
Ottolenghi, Chris [2 ,3 ]
Rauwolf, Kerstin K. [4 ,5 ]
Grebe, Juergen [1 ]
Reunert, Janine [1 ]
Harms, Erik [1 ]
Marquardt, Thorsten [1 ]
机构
[1] Univ Munster, Dept Paediat, Metab Dis, Albert Schweitzer Campus 1, D-48149 Munster, Germany
[2] Univ Paris 05, Inst IMAGINE, Sorbonne Paris Cite, UMR 1163, 24 Blvd Montparnasse, F-75015 Paris, France
[3] Hop Necker Enfants Malad, Biochim Metabol & Prote, 149 Rue Sevres, F-75015 Paris, France
[4] Univ Munster, Dept Pediat Hematol & Oncol, Albert Schweitzer Campus 1, D-48149 Munster, Germany
[5] Univ Childrens Hosp Zurich, Div Pediat Oncol, Steinwiesstr 75, CH-8032 Zurich, Switzerland
关键词
cystinosis; enteric-coated cysteamine; immediate-release cysteamine (Cystagon(& REG; cystine-levels; pharmacokinetics; EXTENDED-RELEASE CYSTEAMINE; PHARMACOKINETICS; CHILDREN; THERAPY; LIFE; FOOD; RAT;
D O I
10.3390/pharmaceutics15071851
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cystinosis is a severe inherited metabolic storage disease caused by the lysosomal accumulation of cystine. Lifelong therapy with the drug cysteamine bitartrate is necessary. Cysteamine cleaves intralysosomal cystine, and thereafter, it can exit from the organelle. The need for frequent dosing every 6 h and the high prevalence of gastrointestinal side effects lead to poor therapy adherence. The purpose of our study was to improve cysteamine treatment by comparing the efficacy of two cysteamine formulas. This is highly relevant for the long-term outcome of cystinosis patients. The cystine and cysteamine levels of 17 patients taking immediate-release cysteamine (IR-cysteamine/Cystagon((R))) and 6 patients taking encapsulated delayed-release cysteamine (EC-cysteamine) were analyzed. The EC-cysteamine levels showed a near-ideal pharmacokinetic profile indicative of delayed release (longer T-max and T-min), and the corresponding cystine levels showed few fluctuations. In addition, the C-max of IR-cysteamine was greater, which was responsible for unbearable side effects (e.g., nausea, vomiting, halitosis, lethargy). Treatment with EC-cysteamine improves the quality of life of cystinosis patients because the frequency of intake can be reduced to 2-3 times daily and it has a more favorable pharmacokinetic profile than IR-cysteamine. In particular, cystinosis patients with no access to the only approved delayed-release cysteamine Procysbi((R)) could benefit from a cost-effective alternative.
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页数:13
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