keyword
MENU ▼
Read by QxMD icon Read
search

Ivacaftor

keyword
https://www.readbyqxmd.com/read/28477428/the-pharmacokinetic-interaction-between-ivacaftor-and-ritonavir-in-healthy-volunteers
#1
Anne Marie Liddy, Gavin McLaughlin, Susanne Schmitz, Deirdre M D'Arcy, Michael G Barry
AIM: The aim of this study was to determine the pharmacokinetic interaction between ivacaftor and ritonavir. METHODS: A liquid chromatography mass spectrometry (LC-MS) method was developed for the measurement of ivacaftor in plasma. An open-label, sequential, cross-over study was conducted with 12 healthy volunteers. Three pharmacokinetic profiles were assessed for each volunteer: ivacaftor 150 mg alone (study A) ivacaftor 150 mg plus ritonavir 50 mg daily (study B) and ivacaftor 150 mg plus ritonavir 50 mg daily after two weeks of ritonavir 50 mg daily (study C)...
May 6, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28445004/cftr-dependent-chloride-efflux-in-cystic-fibrosis-mononuclear-cells-is-increased-by-ivacaftor-therapy
#2
Lorenzo Guerra, Susanna D'Oria, Maria Favia, Stefano Castellani, Teresa Santostasi, Angela M Polizzi, Maria A Mariggiò, Crescenzio Gallo, Valeria Casavola, Pasqualina Montemurro, Giuseppina Leonetti, Antonio Manca, Massimo Conese
AIM: The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) potentiator ivacaftor (Kalydeco®) improves clinical outcome in G551D cystic fibrosis (CF) patients. Here, we have investigated whether ivacaftor has a clinical impact on non-G551D gating mutations and function of circulating leukocytes as well. METHODS: Seven patients were treated with ivacaftor and evaluated at baseline, and at 1-3 and 6 months. Besides clinical and systemic inflammatory parameters, circulating mononuclear cells (MNC) were evaluated for CFTR-dependent chloride efflux by spectrofluorimetry, neutrophils for oxidative burst by cytofluorimetry and HVCN1 mRNA expression by real time PCR...
April 26, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28419121/the-magnitude-of-ivacaftor-effects-on-fluid-secretion-via-r117h-cftr-channels-human-in-vivo-measurements
#3
Jessica E Char, Colleen Dunn, Zoe Davies, Carlos Milla, Richard B Moss, Jeffrey J Wine
We optically measured effects of orally available ivacaftor (Kalydeco®) on sweat rates of identified glands in 3 R117H subjects, each having a unique set of additional mutations, and compared them with 5 healthy control subjects tested contemporaneously. We injected β-adrenergic agonists intradermally to stimulate CFTR-dependent 'C-sweat' and methacholine to stimulate 'M-sweat', which persists in CF subjects. We focused on an R117H-7T/F508del subject who produced quantifiable C-sweat off ivacaftor and was available for 1 blinded, 3 off ivacaftor, and 3 on ivacaftor tests, allowing us to estimate in vivo fold-increase in sweat rates produced by ivacaftor's effect on the open probability (PO) of R117H-CFTR...
2017: PloS One
https://www.readbyqxmd.com/read/28406713/an-observational-study-of-outcomes-and-tolerances-in-patients-with-cystic-fibrosis-initiated-on-lumacaftor-ivacaftor
#4
Mark T Jennings, Rebecca Dezube, Shruti Paranjape, Natalie E West, Gina Hong, Andrew Braun, Jonathan Grant, Christian A Merlo, Noah Lechtzin
RATIONALE: In July 2015, the FDA approved lumacaftor/ivacaftor for use in patients with CF. This drug targets the primary defect in the CFTR protein that is conferred by the F508del CFTR mutation. OBJECTIVE: As there is limited experience with this therapy outside of clinical trials, this study aims to examine the clinical experience of this new drug in a CF population. METHODS: Retrospective cohort study of individuals followed at the Johns Hopkins CF Center, who initiated treatment with lumacaftor/ivacaftor...
April 13, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28371569/pseudomonas-eradication-and-clinical-effectivness-of-ivacaftor-in-four-hispanic-patients-with-s549n
#5
Abigail Strang, Anthony J Fischer, Aaron Chidekel
Ivacaftor was approved for rarer class-III CFTR mutations including S549N in 2014. Since these mutations are uncommon, ongoing reports of patient experiences with Ivacaftor and these mutations are important. This case series describes the clinical effectiveness (including airway infection status, lung function, and growth) of Ivacaftor therapy in four pediatric Hispanic patients with S549N and F508del over 24 months. In these patients, Ivacaftor was highly efficacious with no further Pseudomonas-positive cultures despite prior chronic colonization in three patients as well as notable improvements in lung function and growth...
April 3, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28366727/corrector-vx-809-promotes-interactions-between-cytoplasmic-loop-one-and-the-first-nucleotide-binding-domain-of-cftr
#6
Tip W Loo, David M Clarke
A large number of correctors have been identified that can partially repair defects in folding, stability and trafficking of CFTR processing mutants that cause cystic fibrosis (CF). The best corrector, VX-809 (Lumacaftor), has shown some promise when used in combination with a potentiator (Ivacaftor). Understanding the mechanism of VX-809 is essential for development of better correctors. Here, we tested our prediction that VX-809 repairs folding and processing defects of CFTR by promoting interactions between the first cytoplasmic loop (CL1) of transmembrane domain 1 (TMD1) and the first nucleotide-binding domain (NBD1)...
March 30, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28362199/effects-of-lumacaftor-ivacaftor-in-a-pediatric-cohort-homozygous-for-f508del-cftr
#7
Marie E Egan
No abstract text is available yet for this article.
April 1, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28325531/real-life-initiation-of-lumacaftor-ivacaftor-combination-in-adults-with-cystic-fibrosis-homozygous-for-the-phe508del-cftr-mutation-and-severe-lung-disease
#8
Dominique Hubert, Raphaël Chiron, Boubou Camara, Dominique Grenet, Anne Prévotat, Laurence Bassinet, Stéphane Dominique, Gilles Rault, Julie Macey, Isabelle Honoré, Reem Kanaan, Sylvie Leroy, Nadine Desmazes Dufeu, Pierre-Régis Burgel
OBJECTIVE: To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting. METHODS: A multicentre observational study investigated adverse events, treatment discontinuation, FEV1 and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV1 below 40% predicted. RESULTS: Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment...
May 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28314539/immediate-effects-of-lumacaftor-ivacaftor-administration-on-lung-function-in-patients-with-severe-cystic-fibrosis-lung-disease
#9
Natalia Popowicz, Jamie Wood, Anna Tai, Sue Morey, Siobhain Mulrennan
Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1s [ppFEV1] <40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV1: 34 [31-36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV1 from baseline at 2-hours (median [IQR] relative change: -19 [-21 to -11]%, p<0.001) that persisted at 24-hours but recovered in most patients at 1-month...
May 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28300821/impact-of-cftr-modulation-on-intestinal-ph-motility-and-clinical-outcomes-in-patients-with-cystic-fibrosis-and-the-g551d-mutation
#10
Daniel Gelfond, Sonya Heltshe, Changxing Ma, Steven M Rowe, Carla Frederick, Ahmet Uluer, Leonard Sicilian, Michael Konstan, Elizabeth Tullis, R N Christine Roach, Katherine Griffin, Elizabeth Joseloff, Drucy Borowitz
OBJECTIVES: A defect in bicarbonate secretion contributes to the pathophysiology of gastrointestinal complications in patients with cystic fibrosis (CF). We measured gastrointestinal pH, clinical outcomes, and intestinal transit profiles in patients with the G551D mutation before and after treatment with ivacaftor, a CF transmembrane regulator channel (CFTR) potentiator. METHODS: Observational studies of ivacaftor effectiveness were conducted in the United States and Canada...
March 16, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28222269/restoring-cftr-function-reduces-airway-bacteria-and-inflammation-in-people-with-cystic-fibrosis-and-chronic-lung-infections
#11
Katherine B Hisert, Sonya L Heltshe, Christopher Pope, Peter Jorth, Xia Wu, Rachael M Edwards, Matthew Radey, Frank J Accurso, Daniel J Wolter, Gordon Cooke, Ryan J Adam, Suzanne Carter, Brenda Grogan, Jan L Launspach, Seamas C Donnelly, Charles Gallagher, James E Bruce, David Stoltz, Michael J Welsh, Lucas R Hoffman, Edward F McKone, Pradeep K Singh
RATIONALE: Previous work indicates that ivacaftor improves CFTR activity and lung function in people with cystic fibrosis (CF) and G551D-CFTR mutations, but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once CF lung disease is established. OBJECTIVES: To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with CF and chronic airway infections...
February 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28190780/pregnancy-among-cystic-fibrosis-women-in-the-era-of-cftr-modulators
#12
Sonya L Heltshe, Emily M Godfrey, Tatiana Josephy, Moira L Aitken, Jennifer L Taylor-Cousar
BACKGROUND: Little is known about how new therapies that partially correct the basic cystic fibrosis (CF) defect (ivacaftor and lumacaftor) might alter hormonal contraceptive effectiveness, impact pregnancy outcomes, or affect pregnancy timing. Examination of pregnancy rates among CF women during periods of CFTR modulator therapy initiation will provide foundation for further research in this area. METHODS: The Cystic Fibrosis Foundation Patient Registry was used to examine pregnancy rates and outcomes by genotype class before, during, and after the introduction of CFTR modulator therapies between 2005 and 2014...
February 9, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28143919/growth-in-prepubertal-children-with-cystic-fibrosis-treated-with-ivacaftor
#13
Michael S Stalvey, Jesse Pace, Minoo Niknian, Mark N Higgins, Valerie Tarn, Joy Davis, Sonya L Heltshe, Steven M Rowe
BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) is known for its impact on the lung and pancreas of individuals; however, impaired growth is also a common complication. We hypothesized that targeting the biological defect in the CF transmembrane conductance regulator (CFTR) protein may affect growth outcomes. METHODS: In this post hoc analysis, we assessed linear growth and weight in 83 children (aged 6-11 years) enrolled in 2 clinical trials, the longitudinal-observation GOAL study and the placebo-controlled ENVISION study, to evaluate the effects of ivacaftor, a CFTR potentiator...
February 2017: Pediatrics
https://www.readbyqxmd.com/read/28132845/use-of-hyperpolarized-helium-3-mri-to-assess-response-to-ivacaftor-treatment-in-patients-with-cystic-fibrosis
#14
Talissa A Altes, Mac Johnson, Meredith Fidler, Martyn Botfield, Nicholas J Tustison, Carlos Leiva-Salinas, Eduard E de Lange, Deborah Froh, John P Mugler
BACKGROUND: This pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized (3)He-magnetic resonance imaging (MRI)-defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D-CFTR mutation. METHODS: Part A (single-blind) comprised 4weeks of ivacaftor treatment; Part B (open-label) comprised 48weeks of treatment. The primary outcome was change from baseline in total ventilation defect (TVD; total defect volume:total lung volume ratio)...
March 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28107795/adherence-to-therapies-in-cystic-fibrosis-a-targeted-literature-review
#15
Siva Narayanan, Jochen G Mainz, Smeet Gala, Harold Tabori, Daniel Grossoehme
Cystic fibrosis (CF) is a life-shortening condition with no cure. Available therapies relieving the symptoms of CF are complex and time-consuming. A comprehensive review assessing adherence to different CF therapies, association of adherence with outcomes, and factors influencing adherence could inform optimal patient management strategies. Areas covered: A targeted literature review of studies published from 2010-2016 assessed adherence to CF therapies. Nineteen studies qualified for inclusion. Adherence to CF therapies was sub-optimal, and varied by treatment, mode of treatment administration, age, season, time and method of adherence measurement...
February 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28087700/two-small-molecules-restore-stability-to-a-subpopulation-of-the-cystic-fibrosis-transmembrane-conductance-regulator-with-the-predominant-disease-causing-mutation
#16
Xin Meng, Yiting Wang, Xiaomeng Wang, Joe A Wrennall, Tracy L Rimington, Hongyu Li, Zhiwei Cai, Robert C Ford, David N Sheppard
Cystic fibrosis (CF) is caused by mutations that disrupt the plasma membrane expression, stability, and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. Here, we investigated the impact of these compounds on the instability of F508del-CFTR, the most common CF mutation...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28068001/in-vivo-and-in-vitro-ivacaftor-response-in-cystic-fibrosis-patients-with-residual-cftr-function-n-of-1-studies
#17
Meghan E McGarry, Beate Illek, Ngoc P Ly, Lorna Zlock, Sabrina Olshansky, Courtney Moreno, Walter E Finkbeiner, Dennis W Nielson
RATIONALE: Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, decreases sweat chloride concentration, and improves pulmonary function in 6% of cystic fibrosis (CF) patients with specific CFTR mutations. Ivacaftor increases chloride transport in many other CFTR mutations in non-human cells, if CFTR is in the epithelium. Some CF patients have CFTR in the epithelium with residual CFTR function. The effect of ivacaftor in these patients is unknown. METHODS: This was a series of randomized, crossover N-of-1 trials of ivacaftor and placebo in CF patients ≥8 years old with potential residual CFTR function (intermediate sweat chloride concentration, pancreatic sufficient, or mild bronchiectasis on chest CT)...
April 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28042521/cftr-modulator-therapies-in-pediatric-cystic-fibrosis-focus-on-ivacaftor
#18
Elizabeth L Kramer, John P Clancy
INTRODUCTION: Mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR) cause cystic fibrosis (CF), a disease with life threatening pulmonary and gastrointestinal manifestations. Recent breakthrough therapies restore function to select disease-causing CFTR mutations. Ivacaftor is a small molecule that increases the open channel probability of certain CFTR mutations, producing clear evidence of bioactivity and efficacy in pediatric CF patients. CFTR modulators represent a significant advancement in CF treatment...
October 2016: Expert Opinion on Orphan Drugs
https://www.readbyqxmd.com/read/28012258/functional-defect-of-variants-in-the-adenosine-triphosphate-binding-sites-of-abcb4-and-their-rescue-by-the-cystic-fibrosis-transmembrane-conductance-regulator-potentiator-ivacaftor-vx-770
#19
Jean-Louis Delaunay, Alix Bruneau, Brice Hoffmann, Anne-Marie Durand-Schneider, Véronique Barbu, Emmanuel Jacquemin, Michèle Maurice, Chantal Housset, Isabelle Callebaut, Tounsia Aït-Slimane
ABCB4 (MDR3) is an adenosine triphosphate (ATP)-binding cassette (ABC) transporter expressed at the canalicular membrane of hepatocytes, where it mediates phosphatidylcholine (PC) secretion. Variations in the ABCB4 gene are responsible for several biliary diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3), a rare disease that can be lethal in the absence of liver transplantation. In this study, we investigated the effect and potential rescue of ABCB4 missense variations that reside in the highly conserved motifs of ABC transporters, involved in ATP binding...
February 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28011037/assessment-of-safety-and-efficacy-of-long-term-treatment-with-combination-lumacaftor-and-ivacaftor-therapy-in-patients-with-cystic-fibrosis-homozygous-for-the-f508del-cftr-mutation-progress-a-phase-3-extension-study
#20
Michael W Konstan, Edward F McKone, Richard B Moss, Gautham Marigowda, Simon Tian, David Waltz, Xiaohong Huang, Barry Lubarsky, Jaime Rubin, Stefanie J Millar, David J Pasta, Nicole Mayer-Hamblett, Christopher H Goss, Wayne Morgan, Gregory S Sawicki
BACKGROUND: The 24-week safety and efficacy of lumacaftor/ivacaftor combination therapy was shown in two randomised controlled trials (RCTs)-TRAFFIC and TRANSPORT-in patients with cystic fibrosis who were aged 12 years or older and homozygous for the F508del-CFTR mutation. We aimed to assess the long-term safety and efficacy of extended lumacaftor/ivacaftor therapy in this group of patients in PROGRESS, the long-term extension of TRAFFIC and TRANSPORT. METHODS: PROGRESS was a phase 3, parallel-group, multicentre, 96-week study of patients who completed TRAFFIC or TRANSPORT in 191 sites in 15 countries...
February 2017: Lancet Respiratory Medicine
keyword
keyword
15258
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"