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

World Health Organization. The molecular genetic epidemiology of cystic fibrosis. Report of a joint meeting of WHO/ECFTN/ICF(M)A/ECFS. WHO/HGN/CF/WG/04.02. Geneva, WHO/HGN/CF/WG, 2004.

Goss CH, Quittner AL. Patient-reported outcomes in cystic fibrosis. Proc Am Thorac Soc. 2007;4:378–86.

Pitt TL, Sparrow M, Warner M, Stefanidou M. Survey of resistance of Pseudomonas aeruginosa from UK patients with cystic fibrosis to six commonly prescribed antimicrobial agents. Thorax. 2003;58:794–6.

Stewart PS, Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet. 2007;358:135–8.

Bals R, Hubert D, Tümmler B. Antibiotic treatment of CF lung disease: from bench to bedside. J Cystic Fibrosis. 2011;10(Suppl 2):S146–51.

Hoiby N. New antimicrobials in the management of cystic fibrosis. J Antimicrob Chem. 2002;49:235–8.

Besouw M, Masereeuw R, van den Heuvel L, Levtchenko E. Cysteamine: an old drug with new potential. Drug Discov Today. 2013;18(15/16):785–92.

Charrier C, Rodger C, Robertson J, Kowalczuk A, Shand N, Fraser-Pitt D, Mercer D, O’Neil D. Cysteamine (Lynovex®), a novel mucoactive antimicrobial & antibiofilm agent for the treatment of cystic fibrosis. Orphanet J Rare Dis. 2014;9:189.

Devereux G, Fraser-Pitt, Robertson J, Devlin E, Mercer D, O’Neil D. Cysteamine as a future intervention in cystic fibrosis against current and emerging pathogens: a patient-based ex vivo study confirming its antimicrobial and mucoactive potential in sputum. EBioMedicine. 2015. doi: 10.1016/j.ebiom.2015.08.018 .

Langman CB, Greenbaum LA, Sarwal M, Grimm P, Niaudet P, Deschenes G, Cornelissen E, Morin D, Cochat P, Matossian D, Gaillard S, Bagger MJ, Rioux P. A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: effectiveness on white blood cell cystine levels and comparison of safety. Clin J Am Soc Nephrol. 2012;7:1112–20.

Belldina EB, Huang MY, Schneider JA, Brundage RC, Tracy TS. Steady-state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients. J Clin Pharmacol. 2003;56:520–5.

Bouazza N, Tréluyer JM, Ottolenghi C, Urien S, Deschenes G, Ricquier D, Niaudet P, Chadefaux-Vekemans B. Population pharmacokinetics and pharmacodynamics of cysteamine in nephropathic cystinosis patients. Orphanet J Rare Dis. 2011;6:86.

Dohil R, Cabrera BL, Gangoiti J, Rioux P. The effect of food on cysteamine bitartrate absorption in healthy participants. Clin. Pharmacol. Drug Dev. 2012;1:170–4.

Salvador RA, Davison C, Smith PK. Metabolism of cysteamine. J Pharm Exp Therap. 1957;121:258–65.

Touw DJ, Vinks AA, Mouton JW, Horrevorts AM. Pharmacokinetic optimisation of antibacterial treatment in patients with cystic fibrosis. Current practice and suggestions for future directions. Clin Pharmacokinetics. 1998; 35:437–59.

Cystagon summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000125/WC500037764.pdf . Accessed 10 Apr 2016.

National Research Ethics Service. Safety and progress reports (CTIMPs). http://www.hra.nhs.uk/documents/2013/08/safety-reporting-ctimps-procedural-table.pdf . Accessed 10 Apr 2016.

Guan XHG, Dwivedi C, Matthees DP. A simultaneous liquid chromatography/mass spectrometric assay of glutathione, cysteine, homecysteine and their disulfides in biological samples. J Pharmaceut Biomed Anal. 2003;31:251–61.

Dohil R, Fidler M, Barshop B, Newbury R, Sellers Z, Deutsch R, Schneider J. Esomeprazole therapy for gastric acid hypersecretion in children with cystinosis. Pediatr Nephrol. 2005;20:1786–93.

Pavord ID, Pizzichini MM, Pizzichini E, Hargreave FE. The use of induced sputum to investigate airway inflammation. Thorax. 1997;52:498–501.

Drugbank. Cysteamine. http://www.drugbank.ca/drugs/DB00847 . Accessed 10 Apr 2016.

Palmer KL, Aye LM, Whiteley M. Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum. J Bacteriol. 2007;189:8079–87.

De Stefano D, Villella VR, Esposito S, Tosco A, Sepe A, De Gregorio F, Salvadori L, Grassia R, Leone CA, De Rosa G, Maiuri MC, Pettoello-Mantovani M, Guido S, Bossi A, Zolin A, Venerando A, Pinna LA, Mehta A, Bona G, Kroemer G, Maiuri L, Raia V. Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation. Autophagy. 2014;10:2053–74.

Levtchenko EN, van Dael CM, de Graaf-Hess AC, Wilmer MJ, van den Heuvel LP, Monnens LA, Blom HJ. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006;2006(21):110–3.

Besouw M, Blom H, Tangerman A, de Graaf-Hess A, Levtchenko E. The origin of halitosis in cystinotic patients due to cysteamine treatment. Mol Genet Metab. 2007;2007(91):228–33.

Besouw M, Levtchenko E. Growth retardation in children with cystinosis. Minerva Pediatr. 2010;62:307–14.

UK CF Registry, Annual Data Report 2014. http://www.cysticfibrosis.org.uk/media/1596846/RegistryReport2014.pdf . Accessed 10 2016.