Current Issue : October - December Volume : 2016 Issue Number : 4 Articles : 6 Articles
Purpose This study compared the pharmacokinetics of\nPF-06439535, a potential bevacizumab biosimilar, to bevacizumab\nsourced from the European Union (bevacizumab-\nEU) and USA (bevacizumab-US), and of bevacizumab-EU\nto bevacizumab-US.\nMethods In this double-blind study, 102 healthy males,\naged 21ââ?¬â??55 years, were randomized 1:1:1 to receive a\nsingle 5 mg/kg intravenous dose of PF-06439535, bevacizumab-\nEU, or bevacizumab-US. Pharmacokinetic assessments\nwere conducted for 71 days, with additional safety\nand immunogenicity assessments until day 100. Pharmacokinetic\nsimilarity was achieved if 90 % confidence intervals\n(CIs) for the test-to-reference ratios of the maximum\nserum concentration (Cmax), area under the serum concentrationââ?¬â??\ntime curve from zero to infinity (AUC0ââ?¬â??âË?ž), and\nfrom zero to time of last quantifiable concentration (AUC0ââ?¬â??\nt) were within the 80.00ââ?¬â??125.00 % bioequivalence acceptance\nwindow. Results The three study drugs exhibited similar pharmacokinetic\nproperties. For the comparisons of PF-06439535\nto bevacizumab-EU or bevacizumab-US, and of bevacizumab-\nEU to bevacizumab-US, the 90 % CIs for the\nratios of Cmax, AUC0ââ?¬â??t, and AUC0ââ?¬â??âË?ž were all within\n80.00ââ?¬â??125.00 %. Two, one, and two subjects treated with\nPF-06439535, bevacizumab-EU, and bevacizumab-US,\nrespectively, tested positive for antidrug antibodies, none\nof whom tested positive for neutralizing antibodies. Treatment-\nrelated adverse events were reported in 15.2, 25.7,\nand 18.2 % of subjects in the PF-06439535, bevacizumab-\nEU, and bevacizumab-US treatment arms, respectively.\nConclusions This study demonstrated the pharmacokinetic\nsimilarity of PF-06439535 to both bevacizumab-EU\nand bevacizumab-US, and of bevacizumab-EU to bevacizumab-\nUS. The safety profile (including immunogenicity)\nwas similar in the three treatment groups, with no significant\nsafety findings reported....
Introduction:\nPranlukast is a leukotriene receptor antagonist (LTRA) that is used as an additional controller of mild to moderate asthma. This study\ncompared the efficacy and side effects of two bioequivalent preparations of pranlukast: original pranlukast (OnonÃ?®; Ono\nPharmaceutical, Japan) and a modified formulation of pranlukast (PrakanonÃ?®; Yuhan Co, Korea) in patients with mild to moderate\nasthma.\nMethods:\nOf the 34 subjects screened, 30 patients who were using standard medication to control asthma and scored less than 20 points on the\nAsthma Control Testââ??¢ (ACT) were assigned randomly to one of the two groups in a prospective, open label, crossover study: group 1\nreceived PrakanonÃ?® (150 mg/day) and group 2 received OnonÃ?® (450 mg/day) for 8 weeks each; after a 1-week rest period, the groups\nwere switched to the alternative medication for further 8 weeks and monitored for 2 more weeks without study medication.\nEvaluation parameters included the ACT, quality of life questionnaire adult Korean asthmatics (QLQAKA), pulmonary function\ntests, peripheral blood tests, vital signs, and adverse events.\nResults:\nThirty patients were enrolled and 21 completed the trial: 10 in group 1 and 11 in group 2. The baseline data of the two groups did not\ndiffer. No statistical significant differences were observed in efficacy and lung function at each time and in changes from baseline\nvalue between the two kinds of pranlukast. The final asthma control rate was 81% with PrakanonÃ?® and 76% with OnonÃ?®. There were\nno differences in vital signs and laboratory data at each time and in changes from baseline value between the two drugs. There were\nno differences in adverse events between the two drugs. The most common side effect was abdominal pain. Drug compliance was\nhigh, without differences between the two drugs.\nConclusion:\nThese findings suggest that PrakanonÃ?® which is an improved formulation of pranlukast at a lower dose than the original formulation,\nOnonÃ?®, has a similar efficacy and side effect profile in the control of persistent asthma....
Background: Romiplostim is a peptibody analogue of thrombopoietin (TPO) which regulates platelet production.\nThis molecule consists of two main parts: Peptide sequences which like wild type TPO, mimics stimulation of TPO\nreceptor and IgG1Fc, (Peptide + Antibody = Peptibody). This drug is used in treatment of chronic Immune\nThrombocytopenic Purpura (ITP).\nMethods: In this project E. coli bacteria were transformed by a construct harboring peptibody fusion gene. This\nconstruct consisted of two repeated peptide sequences which have fused to Carboxyl group of IgG1Fc. Designed\nconstruct in E. coli host resulted in protein expression in cytoplasm as inclusion body. The inclusion bodies were\nseparated, washed and after denaturation and solubilization, in the last stage the desired peptibodies were refolded\nand purified. The resulting peptibodies were characterized by SDS-PAGE and Western immunoblotting. The bioactivity\nwere assessed in vivo using subcutaneous injection in mice.\nResults: Results showed accurate molecules were produced and purified. Also, in vivo experiment showed significant\nincrement (more than two fold) of platelets compared to control group.\nConclusion: In this study laboratory scale production of recombinant romiplostim showed proper in-vivo bioactivity.\nThis new approach in expression and purification of this recently introduced thrombopoietin receptor agonist drug\nmay be followed by scale up of its production to response the chronic ITP patient�s demand....
Background: Immunotherapy of patients suffering from the human epidermal growth factor receptor 2 overexpressing\n(HER-2+) breast cancers with the anti-HER-2 antibodies results in increase of the patientsââ?¬â?¢ overall survival.\nHowever, no prophylactic vaccine is available against HER-2+ breast cancers. Although, prophylactic vaccine for\nhuman hepatitis B virus (HBV) is very effective.\nSpecific aim: The specific aim of this work was to design, synthesize, and test bio-molecules which would engage\nprophylactic immunity against hepatitis B virus towards killing breast cancers cells.\nMethods and Results: By biomolecular engineering, we have created a novel family of biomolecules: antibody\n(anti-HER-2) Ã?â?? vaccine (HBsAg) engineered constructs (AVEC: anti-HER-2 Ã?â?? HBsAg). These biomolecules were utilized\nfor redirecting, accelerating, and amplifying of the vaccination-induced, prophylactic immunity originally targeted\nagainst HBV as therapeutic immunity, newly targeted against HER-2+ breast cancers. Treatment of the HER-2+ breast\ncancer cells with AVEC: anti-HER-2 Ã?â?? HBsAg in blood of the patients, vaccinated with HBsAg, rapidly increased efficacy\nof killing of HER-2+ breast cancer cells over that attained with the naked anti-HER-2 antibodies.\nConclusion: Novel antibody-vaccine engineered constructs (AVEC) facilitate redirecting, accelerating, and amplifying\nof prophylactic, HBV vaccination-induced immunity as immunotherapy (RAAVIIT) of HER-2+ breast cancer. We currently\nstreamline this novel therapeutic paradigm into clinical trials of breast and other cancers....
Assessing physician perception of patients with rheumatoid arthritis (RA) they consider as Infliximab-biosimilar-suitable\nmay provide insights into eventual biosimilar adoption in clinical practice settings in Europe. Medical charts of 1204 patients with\nrheumatoid arthritis (RA) from UK/France/Germany/Italy/Spain were abstracted; 425 were identified by physicians as biosimilarinfliximab-\nsuitable; of these, 55% were identified as candidates for being prescribing biosimilar-infliximab. For biosimilar-infliximabsuitable\nYes/No groups, time since diagnosis: 67.1/85.3mo; percentage with moderate/severe disease (per physician judgment):\n46%/40%; ESR:23.4/21.2mm/h; CRP:12.6/8.1mg/dl;VAS(0-10scale):3.7/3.4; Swollen Joint Count:2.6/1.9 and Tender Joint\nCount:4.4/3.1. RA patients considered infliximab-biosimilar not-suitable (per clinical judgment) had been in care for relatively longer\nperiod, had relatively lower disease severity and were less involved in treatment decisions. Physicians were also not readily prepared to\nprescribe the biosimilar to all infliximab-biosimilar-suitable RA patients. Drivers behind observed physician perception warrant\nscrutiny....
The present work aimed to compare the relative bioavailability of Zolapin with 100 mg tablet Leponex as\na reference formulation, through a simple, robust and low-cost bioequivalence assays method. The\nstudy design was multiple-dose, randomized, crossover with patients in steady-state, and was\nperformed with 24 schizophrenic male patients. Subjects received 100 mg twice a day of either Leponex\nor Zolapin for 10 days. At day 10 days of each study phase, blood samples were collected at different\ntimes during 12 h after drug administration and the clozapine concentration was determined by high\nperformance liquid chromatography (HPLC). The individual peak plasma concentrations (Cmax) and the\narea under the concentration-time curve (AUC0-12h) ratios were calculated. The evaluated\npharmacokinetic parameters were quite similar for both formulations. The 90% confidence interval for\nmean ratio of lnCmax (0.9677 to 0.9937) and lnAUC0-12h (0.9811 to 1.0029) were within accepted\ninternational guidelines. The results demonstrate that this methodological approach was able to\nidentify Zolapin as bioequivalent to Leponex when orally administered, both in terms of the rate and\nextent of absorption, and therefore, suitable as a potential low-cost alternative to branded antipsychotic\ndrugs....
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