An Open-Label Investigation of the Pharmacokinetics and Tolerability of Oral Cysteamine in Adults with Cystic Fibrosis

Graham Devereux, Sandra Steele, Kairen Griffiths, Edward Devlin, Douglas Fraser-Pitt, Seonaidh Cotton, John Norrie, Henry Chrystyn, Deborah O'Neil

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14 Citations (Scopus)
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Background and Objective Cysteamine is licensed for use in nephropathic cystinosis but preclinical data suggest a role in managing cystic fibrosis (CF). This study aimed to determine whether oral cysteamine is absorbed in adult CF patients and enters the bronchial secretions. Tolerability outcomes were also explored.Methods Patients ≥18 years of age, weighing >50 kg with stable CF lung disease were commenced on oral cysteamine bitartrate (Cystagon®) 450 mg once daily, increased weekly to 450 mg four times daily. Serial plasma cysteamine concentrations were measured for 24 h after the first dose. Participants were reviewed every week for 6 weeks, except at 4 weeks. Plasma cysteamine concentrations were measured 8 h after dosing when reviewed at 1, 2 and 3 weeks and 6 h after dosing when reviewed at 5 weeks. Sputum cysteamine concentration was also quantified at the 5-week assessment.Results Seven of the ten participants reported adverse reactions typical of cysteamine, two participants discontinued intervention. Following the first 450-mg dose, mean (SD) maximum concentration (C max) was 2.86 (1.96) mg/l, the time corresponding to C max (T max) was 1.2 (0.7) h, the half-life (t ½) was 3.7 (1.7) h, clearance (CL/F) 89.9 (30.5) L/h and volume of distribution (V d/F) 427 (129) L. Cysteamine appeared to accumulate in sputum with a median (interquartile range) sputum:plasma cysteamine concentration ratio of 4.2 (0.98–8.84).Conclusion Oral cysteamine is absorbed and enters the bronchial secretions in patients with CF. Although adverse reactions were common, the majority of patients continued with cysteamine. Further trials are required to establish the risk benefit ratio of cysteamine therapy in CF.
Original languageEnglish
Pages (from-to)605-612
Number of pages8
JournalClinical Drug Investigation
Issue number8
Early online date6 May 2016
Publication statusPublished - Aug 2016

Bibliographical note

Trial Steering Committee: Dr Steve Cunningham (chair), Dr Stephen Bourke, Dr Gordon MacGregor.
We are grateful to all the participants who took part in the study. We are also grateful to the support from the Clinical Trials Pharmacy at Aberdeen Royal Infirmary.

Role of the funding source
This study was funded by Health Sciences Scotland (West Medical Building, University Avenue, Glasgow G12 8QQ. UK) and the Cystic Fibrosis Trust (One Aldgate, London. EC3N 1RE. UK). The funders did not contribute to study design, data collection, analysis, this report or the decision to publish.


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