title: An Open-Label Investigation of the Pharmacokinetics and Tolerability of Oral Cysteamine in Adults with Cystic Fibrosis.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cystic Fibrosis Clinic, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK. g.devereux@abdn.ac.uk.|Child Health, Royal Aberdeen Children's Hospital, Aberdeen, AB25 2ZG, UK. g.devereux@abdn.ac.uk.
authors.forename: Graham
authors.initials: G
authors.lastname: Devereux
authors.affiliation: Cystic Fibrosis Clinic, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Steele
authors.affiliation: Cystic Fibrosis Clinic, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK.
authors.forename: Kairen
authors.initials: K
authors.lastname: Griffiths
authors.affiliation: Cystic Fibrosis Clinic, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK.|Novabiotics Ltd, Cruickshank Building, Craibstone, Aberdeen, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Devlin
authors.affiliation: Novabiotics Ltd, Cruickshank Building, Craibstone, Aberdeen, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Fraser-Pitt
authors.affiliation: Centre for Healthcare Randomised Trials, University of Aberdeen, Health Sciences Building, Foresterhill, Aberdeen, UK.
authors.forename: Seonaidh
authors.initials: S
authors.lastname: Cotton
authors.affiliation: Centre for Healthcare Randomised Trials, University of Aberdeen, Health Sciences Building, Foresterhill, Aberdeen, UK.
authors.forename: John
authors.initials: J
authors.lastname: Norrie
authors.affiliation: Talmedica Ltd, St Crispin House, St Crispin Way, Haslingden, Rossendale, UK.
authors.forename: Henry
authors.initials: H
authors.lastname: Chrystyn
authors.affiliation: Novabiotics Ltd, Cruickshank Building, Craibstone, Aberdeen, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: O'Neil
mesh_terms: D000328:Adult; D019540:Area Under Curve; D003543:Cysteamine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D003554:Cystinosis / Q000188:drug therapy; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D013183:Sputum / Q000378:metabolism / Q000382:microbiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003543:Cysteamine