Abstract:
BACKGROUND:Recombinant activated factor VII (rFVIIa) is indicated to treat bleeding episodes or prevent bleeding related to surgery in patients with hemophilia A or B who have antibodies to coagulation factors VIII or IX. The first-generation rFVIIa formulation is stable when stored under refrigeration. A new formulation has been developed for storage at room temperature, which may improve patients' access to treatment during bleeding episodes. OBJECTIVE:These in vitro experiments were conducted to evaluate the stability of the new formulation of rFVIIa, both lyophilized and reconstituted, under the expected storage conditions, as well as at higher temperatures. METHODS:The stability of the new rFVIIa formulation when stored under various conditions before and after reconstitution was evaluated in terms of retained activity (clotting assay), rFVIIa content (high-performance liquid chromatography [HPLC]), and rFVIIa degradation products (HPLC), including aggregates (dimer/oligomer). Activity was analyzed within specific limits representing the allowable minimum/maximum for each test parameter at the end of the product's shelf-life, as adopted by the European Medicines Agency and the US Food and Drug Administration. Before reconstitution, vials from 9 lots of the new rFVIIa formulation, 3 of each size (1, 2, and 5 mg/vial), were stored at refrigerated temperature (5 degrees C) and at room temperature (25 degrees C) for 24 months, and at 30 degrees C for 12 months. To simulate short-term exposure to temperatures higher than recommended, samples were stored at 40 degrees C for 6 months, followed by storage at 25 degrees C for 12 months. To simulate the home setting, in which the product may be alternately stored in and out of the refrigerator, samples were stored at 30 degrees C for 8 hours and then at 5 degrees C for 16 hours, repeated daily for 5 days. To analyze the effect of storage at extremely elevated temperatures, samples were exposed to temperatures of 50 degrees C, 60 degrees C, and 70 degrees C for 12 hours. After reconstitution, samples were maintained at 25 degrees C for up to 6 hours or at 5 degrees C for up to 24 hours. RESULTS:The specific activity and rFVIIa content of the new lyophilized formulation remained stable after storage for 24 months at 5 degrees C and 25 degrees C, and for 12 months at 30 degrees C; after 5 days of daily alternation between storage at 5 degrees C and 30 degrees C; and after storage for 6 months at 40 degrees C followed by 12 months at 25 degrees C. When stored at 50 degrees C and 60 degrees C for 12 hours, activity remained constant, whereas rFVIIa aggregates increased within the specified limits; after storage at 70 degrees C for 12 hours, rFVIIa activity decreased in parallel with the formation of aggregates, which exceeded the specified limit for the 5-mg product. After reconstitution, samples of all vial sizes of the new rFVIIa formulation retained their activity when stored at 25 degrees C for 6 hours and at 5 degrees C for 24 hours. CONCLUSIONS:In these in vitro experiments, the new lyophilized formulation of rFVIIa was stable when stored for 24 months at 25 degrees C, 12 months at 30 degrees C, 6 months at 40 degrees C, and 12 hours at 50 degrees C and 60 degrees C without compromise to its activity or rFVIIa content. The reconstituted product retained activity when stored at 25 degrees C for 6 hours and at 5 degrees C for 24 hours.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Nedergaard H,Vestergaard S,Jensen PT,Kristiansen MW,Jensen MB,Ostergaard PB,Norsell T,Bjerre Jdoi
10.1016/s0149-2918(08)80055-0subject
Has Abstractpub_date
2008-07-01 00:00:00pages
1309-15issue
7eissn
0149-2918issn
1879-114Xpii
S0149-2918(08)80055-0journal_volume
30pub_type
杂志文章abstract::General health-status questionnaires such as the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) are frequently used to measure health-related quality of life. The SF-36, in its current form, cannot be used to measure individuals' utilities or preferences for their health state. Recently, several inves...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)86747-8
更新日期:1999-11-01 00:00:00
abstract:BACKGROUND:Danazol is a synthetic androgen derivative frequently used as prophylaxis in patients with hereditary angioedema (HAE) due to complement-1 esterase inhibitor deficiency. However, danazol has been reported to decrease high-density lipoprotein cholesterol (HDL-C) levels and to adversely affect coagulation para...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2008.12.021
更新日期:2008-12-01 00:00:00
abstract::Faced with rising drug costs and an increase in type-1 beta-lactamase resistance, hospitals have been looking for ways to contain antibiotic costs while continuing to provide quality medical care. The hospital pharmacy at Montefiore Medical Center, Moses Division, has developed a number of programs aimed at identifyin...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND:Panitumumab, formerly known as ABX-EGF, was the first recombinant human immunoglobulin G2 monoclonal antibody approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing metastatic colorectal cancer (mCRC) refractory to fluoropyrimidine-, oxa...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2008.01.014
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:It has been reported that the efficacy of acute forms of nicotine replacement therapy, such as nicotine gum and lozenges, improves when sufficient quantities of medication are used. OBJECTIVE:This analysis examined whether adherence with daily nicotine patch wear was associated with improved rates of smokin...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2008.09.016
更新日期:2008-10-01 00:00:00
abstract::The comparative bioavailability of ceftibuten, a new third-generation cephalosporin antibiotic given orally once daily, in capsule and suspension dosage forms, was assessed in healthy male subjects. In three separate studies, subjects received either a 400-mg dose as a suspension or one laboratory-batch, 400-mg capsul...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0149-2918(96)80068-3
更新日期:1996-11-01 00:00:00
abstract::Two groups of patients with idiopathic Parkinson's disease underwent quantified electroencephalography (EEGq) using fast Fourier transfer to assess the effects of treatment with citicholine. Evidence of cortical cognitive impairment was seen in one group but not in the other. Certain parameters were established which ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract:PURPOSE:The effects of air pollutants have been receiving increased attention both clinically and in the media. One such pollutant is mold, fungal growth in the form of multicellular filaments known as hyphae. The growth of molds is omnipresent not only in outdoor settings but also in indoor environments containing exc...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2018.05.004
更新日期:2018-06-01 00:00:00
abstract:PURPOSE:Improvement in health behaviors following cancer diagnosis may contribute to better prognosis and well-being. This study examines the prevalence of health behaviors in cervical cancer survivors who have completed treatment, and associations between health behaviors and quality of life (QOL). METHODS:We recruit...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2016.02.006
更新日期:2016-03-01 00:00:00
abstract::A large number of medications and medical devices removed from the market by the US Food and Drug Administration over the past 4 decades specifically posed greater health risks to women. This article reviews the historical background of sex and gender in clinical research policy and describes several approved drugs an...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2016.12.009
更新日期:2017-01-01 00:00:00
abstract::The antiemetic efficacy and tolerability of four different oral doses of granisetron (0.25, 0.5, 1, and 2 mg twice daily [BID]) were compared in a randomized, double-blind, parallel-group, multicenter study involving 930 patients with malignant disease receiving moderately emetogenic chemotherapy over a 7- or 14-day p...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/0149-2918(95)80005-0
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND:Vitamin B12 (cobalamin) deficiency may be caused by inadequate dietary intake of B12 or by conditions that result in malabsorption of the vitamin. Crystalline vitamin B12, usually in the form of cyanocobalamin, is administered parenterally (ie, intramuscularly) or orally for treating deficiency states. Intra...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2011.05.088
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:The continuing increase in the rate of penicillin and cephalosporin resistance among respiratory pathogens and of cross-resistance to macrolide antibiotics has led to the recommendation that fluoroquinolone antibiotics be used to treat high-risk patients with community-acquired pneumonia (CAP) and acute bact...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/S0149-2918(00)89007-4
更新日期:2000-04-01 00:00:00
abstract::We investigated the usefulness of the C64 quantitative tuning fork in assessing vibratory sensation in patients with diabetic neuropathy. The vibratory sensation scores determined by using the C64 quantitative tuning fork were significantly correlated with severity of subjective symptoms of numbness, cold, desensitiza...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND:According to evidence-based guidelines, the combination of inhaled corticosteroids and inhaled long-acting beta(2)-agonists in a single inhaler is recommended for patients with chronic obstructive pulmonary disease (COPD) who are experiencing exacerbations. The relative effectiveness of combination products ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.06.022
更新日期:2010-07-01 00:00:00
abstract:PURPOSE:Megestrol acetate oral suspension is an appetite stimulant indicated for cachexia. It is available in a conventional formulation and as a nanocrystal dispersion. The aim of this study was to compare the tolerability and pharmacokinetics of these formulations under fed conditions in healthy Korean volunteers. M...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2014.09.022
更新日期:2015-02-01 00:00:00
abstract:PURPOSE:A combination of clopidogrel and aspirin is the standard treatment for patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. Two novel antiplatelet agents, ticagrelor and prasugrel, have been shown to rapidly and more effectively inhibit the P2Y12 receptor compared with ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2015.01.010
更新日期:2015-03-01 00:00:00
abstract:PURPOSE:Long-acting insulin analogues were developed to facilitate consistent glycemic control without excessive hypoglycemia. However, structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors. The aim of this study was to estimate the risk of s...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.06.031
更新日期:2014-09-01 00:00:00
abstract::The objective of this study was to assess a weight-based heparin (WBH) nomogram (80-U/kg bolus, 18-U/kg-per-hour initial infusion) and determine its clinical performance and impact on resource utilization. All patients treated with heparin for venous thromboembolism or unstable angina during a 15-week study period wer...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/s0149-2918(98)80133-1
更新日期:1998-07-01 00:00:00
abstract:OBJECTIVE:The goal of this study was to compare the efficacy and safety profiles of biphasic insulin aspart 30 (30% soluble insulin aspart and 70% protaminated insulin aspart [BIAsp 30]) and biphasic insulin lispro 25 (25% soluble insulin lispro and 75% neutral protamine lispro [Mix25]) used in a BID injection regimen ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(04)90055-0
更新日期:2004-04-01 00:00:00
abstract:BACKGROUND:On February 3, 2006, the US Food and Drug Administration (FDA) approved a live, oral, pentavalent (G1-G4, P1[8]) human-bovine reassortant rotavirus vaccine for the prevention of rotavirus gastroenteritis (RVGE) in infants in the United States. The Advisory Committee of Immunization Practices of the Centers f...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2007.12.018
更新日期:2007-12-01 00:00:00
abstract:PURPOSE:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis compared the efficacy and safety of tofacitinib with biologic disease-modifying antirheumatic drugs in patients with RA and a prior inadequate response (IR) to tumor necrosis factor inhibitors (TNFi). ME...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2016.11.004
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:The real-world clinical effectiveness of exogenous insulin is limited by nonadherence. Various insulin delivery systems have been developed to help improve adherence, with prefilled pens gaining popularity among adult Singaporeans with diabetes. However, adherence to insulin in people with diabetes in Singap...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.05.009
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:The off-label use of beta-blockers might be prevalent, but no studies have provided empiric data on the off-label use based on utilization data. OBJECTIVE:This secondary data analysis was conducted to describe the trends of off-label use of beta-blockers among ambulatory visits made to office-based physicia...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2006.10.015
更新日期:2006-10-01 00:00:00
abstract:PURPOSE:Rosuvastatin, a hydroxy methylglutaryl coenzyme A reductase inhibitor; telmisartan, an angiotensin receptor blocker; and amlodipine, a calcium channel inhibitor, are commonly prescribed together for the treatment of hypertension nonresponsive to monotherapy and accompanied by dyslipidemia. However, the pharmaco...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2016.06.011
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Treatment of infections caused by gram-negative bacilli is increasingly challenging because of emerging resistance. Current surveillance data are informative, but may not discern differences by infection site and clinical setting, and do not incorporate pharmacodynamic (PD) characteristics when determining s...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clinthera.2009.11.021
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:Interferon (IFN) alfa is a clinically effective therapy used in a wide range of viral infections and cell-proliferative disorders. Combination therapy with IFN alfa-2b and ribavirin is the current standard of care for the treatment of chronic hepatitis C (CHC) infection. However, standard IFN alfa has the dr...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(02)80042-x
更新日期:2002-09-01 00:00:00
abstract:BACKGROUND:Pitavastatin, a fully synthetic β-hydroxy-β-methylglutaryl-coenzyme A reductase inhibitor, is potent for the treatment of primary hyperlipidemia and mixed dyslipidemia. Recently, the original product and some generic products of pitavastatin calcium have become available in China. However, the intrasubject v...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.06.021
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND:Mycophenolate mofetil (MMF) is an immunosuppressant indicated for prophylaxis of acute organ transplant rejection. Generic MMF is less costly than the branded product, but European regulatory authorities require bioequivalence studies for the marketing of generics. OBJECTIVES:The aims of the 2 studies repor...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2011.04.003
更新日期:2011-03-01 00:00:00
abstract::This paper briefly reviews the extent of current drug coverage for Medicare beneficiaries and describes the most important issues faced by aged beneficiaries who receive or seek drug coverage through a Medicare managed care plan. Changes in payment rates to these plans as a result of the Balanced Budget Act of 1997 ma...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(98)80123-9
更新日期:1998-11-01 00:00:00