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Ravi Gupta, Thomas J Bollyky, Matthew Cohen, Joseph S Ross, Aaron S Kesselheim
OBJECTIVES: To evaluate whether off-patent prescription drugs at risk of sudden price increases or shortages in the United States are available from independent manufacturers approved in other well regulated settings around the world. DESIGN: Observational study. SETTING: Off-patent drugs in the USA and approved by the Food and Drug Administration, up to 10 April 2017. STUDY COHORT: Novel tablet or capsule prescription drugs approved by the FDA since 1939 that were no longer protected by patents or other market exclusivity and had up to three generic versions...
March 19, 2018: BMJ: British Medical Journal
Jacques Rottembourg, Guy Rostoker
Generic immunosuppressive drugs are available in Europe Canada and the United States. Between countries, there are large differences in penetration of generic drugs in general, and for immunosuppressive drugs in particular. The registration for generic immunosuppressive drugs are slightly different, but the criteria for registration of narrow therapeutic index drugs and bioequivalence studies, performed only in healthy volunteers, will remain in the medical landscape. About 50 studies compare the clinical efficacy and bioequivalence of the generic immunosuppressive drugs in patients with solid organ transplants...
March 16, 2018: La Presse Médicale
Yunona Khomitskaya, Nadezhda Tikhonova, Konstantin Gudkov, Svetlana Erofeeva, Victoria Holmes, Brian Dayton, Nigel Davies, David W Boulton, Weifeng Tang
PURPOSE: Fixed-combination drug products (FCDPs) combining dapagliflozin and metformin extended release (XR) may provide patients with type 2 diabetes mellitus with an alternative antihyperglycemic treatment, which could improve adherence by reducing tablet burden. This study evaluated the bioequivalence of dapagliflozin/metformin XR FCDP versus the co-administration of the individual monotherapy tablets currently available for use in the Russian Federation. METHODS: Healthy subjects aged 18 to 45 years were enrolled in this randomized, open-label, 2-period crossover study, conducted in a single Russian center...
March 13, 2018: Clinical Therapeutics
Patrick Darken, Paolo DePetrillo, Colin Reisner, Earl St Rose, Paul Dorinsky
The budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) is an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2 -agonist fixed-dose combination formulated with innovative co-suspension delivery technology that is in clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, Phase I, single-dose, six-treatment, four-period, crossover study (NCT01980615) examined the pharmacokinetic (PK) and safety profile of three doses of BGF MDI (320/14...
March 12, 2018: Pulmonary Pharmacology & Therapeutics
Tom Ottoboni, Mary Rose Keller, Matt Cravets, Neil Clendeninn, Barry Quart
Introduction: Fosaprepitant, an intravenous (IV) aprepitant prodrug for chemotherapy-induced nausea and vomiting prophylaxis, is associated with systemic and infusion-site reactions attributed in part to its surfactant, polysorbate 80. HTX-019 is an IV aprepitant formulation free of polysorbate 80 and other synthetic surfactants. Materials and methods: This open-label, single-dose, randomized, two-way crossover bioequivalence study compared pharmacokinetics and safety of HTX-019 and fosaprepitant...
2018: Drug Design, Development and Therapy
Claudia Miranda, Zenia Pérez-Rodríguez, Rosario Hernández-Armengol, Yaidel Quiñones-García, Tania Betancourt-Purón, Miguel Ángel Cabrera-Pérez
The aim of the present study is to contribute to the scientific characterization of sildenafil citrate according to the Biopharmaceutics Classification System, following the World Health Organization (WHO) guidelines for biowaivers. The solubility and intestinal permeability data of sildenafil citrate were collected from literature; however, the experimental solubility studies are inconclusive and its "high permeability" suggests an API in the borderline of BCS Class I and Class II. The pH-solubility profile was determined using the saturation shake-flask method over the pH range of 1...
March 12, 2018: AAPS PharmSciTech
Ying Peng, Qingqing Chang, Na Yang, Shiyin Gu, Yi Zhou, Lifang Yin, Jiye Aa, Guangji Wang, Jianguo Sun
A simple, sensitive and specific hydrophilic interaction liquid chromatography coupled to electrospray ionization mass spectrometric (HILIC-MS) method was developed and validated to determine the plasma concentrations of metformin, saxagliptin and 5-hydroxy saxagliptin simultaneously in clinical studies. Plasma samples were first acidified and then protein precipitated with acetonitrile. Chromatographic separation was achieved on a HILIC Chrom Matrix HP amide column (5 μm, 3.0 × 100 mm I.D.). The mobile phase consisted of acetonitrile and 5 mM ammonium formate buffer containing 0...
February 27, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Stanley B Cohen, Alberto Alonso-Ruiz, Piotr A Klimiuk, Eric C Lee, Nuala Peter, Ivo Sonderegger, Deepak Assudani
OBJECTIVE: To demonstrate clinical equivalence of adalimumab biosimilar candidate BI 695501 with Humira. METHODS: Patients with active rheumatoid arthritis on stable methotrexate were randomised to BI 695501 or Humira in a double-blind, parallel-group, equivalence study. At week 24, patients were rerandomised to continue BI 695501 or Humira, or switch from Humira to BI 695501. The coprimary endpoints were the percentage of patients achieving the American College of Rheumatology 20% response criteria (ACR20) at weeks 12 and 24...
March 7, 2018: Annals of the Rheumatic Diseases
Sarah A Morrow, J Alexander Fraser, Chad Day, Denise Bowman, Heather Rosehart, Marcelo Kremenchutzky, Michael Nicolle
Importance: Intravenous (IV) administration of corticosteroids is the standard of care in the treatment of acute optic neuritis. However, it is uncertain whether a bioequivalent dose of corticosteroid administered orally, which may be more cost-efficient and convenient for patients, is as effective as IV administration in the treatment of acute optic neuritis. Objective: To determine whether recovery of vision following treatment of acute optic neuritis with a high-dose IV corticosteroid is superior to that with a bioequivalent dose of an oral corticosteroid...
March 5, 2018: JAMA Neurology
Frank Karkossa, Sandra Klein
Drug release and availability at the site of action are the major factors determining the clinical response for locally-acting gastrointestinal (GI) drug products. The present work focused on the prediction of site and extent of in vivo mesalazine release after oral administration to a variety of subjects using individualized in vitro drug release experiments. First, experiments mimicking GI passages in average adult subjects were performed. Then, results from a study screening fasted in vivo pH- and transit profiles in individual subjects were translated into a novel in vitro dissolution model enabling to mimic individual GI pH-profiles and transit times with physiologically relevant dissolution media...
February 27, 2018: Journal of Pharmaceutical Sciences
Mamdouh R Rezk, Kamal A Badr
A robust, rapid and sensitive UPLC-MS/MS method has been developed, optimized and validated for determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple-reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC-MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using Acquity UPLC BEH C18 (50 x 2.1 mm, 1.7 μm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0...
March 2, 2018: Biomedical Chromatography: BMC
Merja Kirjavainen, Leena Mattila, Mikko Vahteristo, Jani Korhonen, Satu Lähelmä
BACKGROUND: Easyhaler® dry powder inhaler (DPI) containing salmeterol and fluticasone propionate was developed for the treatment of asthma and chronic obstructive pulmonary disease. Three different Salmeterol/fluticasone Easyhaler test products (Orion Pharma, Finland) were compared against the reference product Seretide® Diskus® DPI (GlaxoSmithKline, United Kingdom) to study whether any of the test products are bioequivalent with the reference. METHODS: Open and randomized pharmacokinetic four-period crossover study on 65 healthy volunteers was performed in a single center to compare the lung deposition and total systemic exposure of salmeterol and fluticasone propionate after administration of single doses (two inhalations of 50/500 μg/inhalation strength) in fasting conditions...
March 1, 2018: Journal of Aerosol Medicine and Pulmonary Drug Delivery
Ahmed U Mishuk, Jingjing Qian, Jennifer N Howard, Ilene Harris, Gavriella Frank, Zippora Kiptanui, Richard Hansen
BACKGROUND: Generic drugs are bioequivalent and cost-effective alternatives to brand drugs. In 2014, $254 billion was saved because of the use of generic drugs in the United States. OBJECTIVE: To critically assess evidence on the association between patient characteristics and generic drug use in order to inform the development of educational outreach for improving generic drug use among patients. METHODS: We systematically searched the literature between January 2005 and December 2016 using PubMed, Web of Science, Ovid MEDLINE, Google Scholar, and EBSCO IPA-MEDLINE for potentially relevant studies...
March 2018: Journal of Managed Care & Specialty Pharmacy
Sumalatha Nallagundla, Srinivas Patnala, Isadore Kanfer
This study indicates the application of tape stripping (TS) for bioequivalence (BE) assessment of a topical cream product containing 5% acyclovir. A TS method, previously used successfully to assess BE of topical clobetasol propionate and clotrimazole formulations, was used to assess BE of an acyclovir cream (5%) formulation as well as a diluted acyclovir formulation (1.5%) applied to the skin of healthy humans. An appropriate application time was established by conducting a dose duration study using the innovator product, Zovirax® cream...
February 26, 2018: AAPS PharmSciTech
P J Garcia-Ruiz, P Sanz-Cartagena, J C Martinez-Castrillo, B Ares-Pensado, I Aviles-Olmos, M Blazquez-Estrada, S Fanjul-Arbos, J Garcia-Caldentey, J Gazulla, J Gutierrez-Garcia, B Huete-Anton, C Lucas-Rodenas, M R Luquin, I Martinez-Torres, P Medialdea-Natera, A Mendoza-Rodriguez, P Mir-Rivera, I J Posada, J Ruiz-Martinez, P Sanchez-Alonso, J M Trejo-Gabriel Y Galan, L Vela, J L Pena-Segura
INTRODUCTION: Botulinum toxin type A (BTA) is a bacterial endotoxin, whose therapeutic use has had a dramatic impact on different neurological disorders, such as dystonia and spasticity. AIM: To analyze and summarize different questions about the use of BTA in our clinical practice. DEVELOPMENT: A group of experts in neurology developed a list of topics related with the use of BTA. Two groups were considered: neuropharmacology and dystonia...
March 1, 2018: Revista de Neurologia
Antonello Di Paolo, Elena Arrigoni
Generic drugs are important components of measures introduced by healthcare regulatory authorities to reduce treatment costs. In most patients and conditions the switch from a branded drug to its generic counterpart is performed with no major complications. However, evidence from complex diseases suggests that generic substitution requires careful evaluation in some settings and that current bioequivalence criteria may not always be adequate for establishing the interchangeability of branded and generic products...
February 20, 2018: Drugs
Willi Maurer, Byron Jones, Ying Chen
In a 2×2 crossover trial for establishing average bioequivalence (ABE) of a generic agent and a currently marketed drug, the recommended approach to hypothesis testing is the two one-sided test (TOST) procedure, which depends, among other things, on the estimated within-subject variability. The power of this procedure, and therefore the sample size required to achieve a minimum power, depends on having a good estimate of this variability. When there is uncertainty, it is advisable to plan the design in two stages, with an interim sample size reestimation after the first stage, using an interim estimate of the within-subject variability...
February 20, 2018: Statistics in Medicine
Thalita Pedon de Araujo, Isabelle Moura Fittipaldi, Danilo Cesar Galindo Bedor, Maira Ludna Duarte, Sarah F Cordery, Richard H Guy, M Begonã Delgado-Charro, Davi Pereira de Santana, Leila Bastos Leal
The topical bioavailabilities of metronidazole from a commercially available 'reference' product (Rozex® ) and two extemporaneous test formulations were compared. With the reference drug product, a full skin pharmacokinetic profile, in vivo in human volunteers (following a 6-hour uptake and clearance over the subsequent 22 hours), was obtained using an improved stratum corneum (SC) sampling procedure. Then, a two-time point SC sampling method enabled the bio(in)equivalence of the test formulations to Rozex® to be evaluated...
February 17, 2018: International Journal of Pharmaceutics
Julia Schnorr, Sören Fütterer, Karsten Spicher, Maria Catarinolo, Christoph Schlösser, Harald Enzmann, Peter Langguth
Although parenteral iron products have been established to medicinal use decades before, their structure and pharmacokinetic properties are not fully characterized yet. With its' second reflection paper on intravenous iron-based nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency provided an extensive catalogue of methods for quality, non-clinical and pharmacokinetic studies for the comparison of nano-sized iron products to an originator (EMA, 2015). For iron distribution studies, the reflection paper assumed the use of rodents...
February 15, 2018: Regulatory Toxicology and Pharmacology: RTP
Ashima Bhatia, Shraddha Tawade, Mushtaque Mastim, Eliford Ngaimisi Kitabi, Mathangi Gopalakrishnan, Manish Shah, Sridhar Yeshamaina, Joga Gobburu, Maharaj Sahib, Dipak Thakur, K M Prasanna Kumar
AIMS: The objective of the study was to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of an insulin glargine formulation, Glaritus ® (test) with the innovator's formulation Lantus ® (reference) using the euglycemic clamp technique in a single-dose, double-blind, randomized, two sequences, four-period replicate crossover study in healthy volunteers (n = 40). METHODS: Subjects received subcutaneous administration of the insulin glargine (0...
February 16, 2018: Acta Diabetologica
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