ABCMdb

PMID: 22739718

Pettit RS
Cystic fibrosis transmembrane conductance regulator-modifying medications: the future of cystic fibrosis treatment.
Ann Pharmacother. 2012 Jul-Aug;46(7-8):1065-75. Epub 2012 Jun 26., [PubMed]

Sentences

No. Mutations Sentence Comment

12 ABCC7 p.Gly551Asp Ivacaftor is a new CFTR potentiator that helps the CFTR channel open properly in patients with the CFTR mutation, G551D. Login to comment 14 ABCC7 p.Gly551Asp Ivacaftor was approved by the Food and Drug Administration (FDA) to be taken orally at a dose of 150 mg twice a day in G551D CF patients older than 6 years. Login to comment 49 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp Ivacaftor Ivacaftor is an oral CFTR potentiator that increases CFTR channel opening.10 Ivacaftor has been shown to increase CFTR channel opening in vitro in both G551D and F508del mutation cells.10 Although the exact mechanism by which ivacaftor opens the CFTR channel is not known, in vitro ivacaftor increased apical surface fluid and cilia beating.10 Following in vitro studies, ivacaftor was investigated in humans with CF, with both G551D and F508del mutations. Login to comment 50 ABCC7 p.Gly551Asp A 2-part study in 39 adults with CF, with at least 1 copy of G551D and mild to moderate lung disease, tested different doses of ivacaftor (25, 75, 150, and 250 mg) twice daily versus placebo11 (Table 1). Login to comment 92 ABCC7 p.Gly551Asp Ivacaftor has been studied primarily in patients with a G551D mutation, but it has also been studied in patients with the most common CFTR defect, F508del15 (Table 1). Login to comment 95 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp Ivacaftor therapy resulted in dramatic improvements in CFTR function in patients with G551D, a class III mutation, and was approved by the FDA on January 31, 2012, for patients with at least 1 G551D mutation who are older than 6 years.17 The approved dose is 150 mg in tablet form, taken orally twice a day; the tablet should be swallowed whole. Login to comment 116 ABCC7 p.Arg117His Future research for ivacaftor includes use in other gating CFTR mutations (class III mutations),20 use in patients between ages 2 and 5 years, and patients with at least 1 copy of R117H mutation, a class IV mutation.21 Clinicians should monitor the literature to determine whether ivacaftor should be used in patients with CF and other genotypes. Login to comment 140 ABCC7 p.Gly542* Ataluren not only has therapeutic applicability in patients with CF and class I CFTR mutations, but may be effective in other diseases, such as Duchenne muscular dystrophy.27 Ataluren was originally studied in a mouse model, where it restored chloride to 24-29% of normal levels in mice with CF and a G542X mutation.28 Following positive animal studies, ataluren was administered to 62 healthy adults in increasing doses, from 3 mg/kg to 200 mg/kg per dose.29 The doses were well tolerated until more than 150 mg/kg was administered; these doses caused headache, dizziness, and gastrointestinal adverse effects. Login to comment 165 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp Ivacaftor, an oral potentiator, has shown dramatic results in decreasing sweat chloride and improving FEV1 in patients with G551D CFTR mutations and is FDA approved for use in G551D patients older than 6 years. Login to comment 200 ABCC7 p.Gly551Asp Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med 2010;363:1991-2003. Login to comment 202 ABCC7 p.Gly551Asp Ramsey BW, Davies J, McElvaney G, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011; 365:1663-72. Login to comment 208 ABCC7 p.Gly551Asp Aherns R, Rodriguez S, Yen K, et al. VX-770 in subjects 6 to 11 years with cystic fibrosis and the G551D-CFTR mutation (abstract) Pediatr Pulmonol 2011;(suppl 34):283. Login to comment 246 ABCC7 p.Gly542* Du M, Liu X, Welch EM, et al. PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Login to comment 266 ABCC7 p.Gly551Asp Ivacaftor es un potenciador nuevo de la CFTR que ayuda a mantener el canal de la CFTR abierto en pacientes con la mutación G551D. Login to comment 268 ABCC7 p.Gly551Asp La FDA aprobó Ivacaftor para usarse en dosis oral de 150 mg 2 veces al día en pacientes con fibrosis quística con la mutación G551D mayores de 6 años. Estudios futuros están investigando el uso de ivacaftor en otros tipos de mutación de activación periódica y en pacientes más jóvenes. Login to comment 283 ABCC7 p.Gly551Asp L`ivacaftor est un nouveau potentialisateur de la RCTF qui permet aux canaux RCTF de s`ouvrir adéquatement chez les patients qui présentent une mutation RCTF G551D. Login to comment 285 ABCC7 p.Gly551Asp L`ivacaftor a été approuvé par la FDA à la dose de 150 mg pris par la bouche 2 fois par jour chez les patients atteints de FK et de la mutation G551D, âgés de plus de 6 ans. Les études à venir portent sur l`utilisation de l`ivacaftor chez les patients présentant d`autres mutations et chez des patients plus jeunes. Login to comment