Current Issue : January - March Volume : 2018 Issue Number : 1 Articles : 5 Articles
Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat\nis its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat\nanalysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed\nand validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as\ninternal standard (IS). The method was accurate for the within- and between-days analysis, and precise CV% was <5%, being linear\nover the calibration range 1.0ââ?¬â??200.0 ng/ml. Stability was >85%and the LODwas 0.907 and 0.910 ng/ml for enalapril and enalaprilat,\nrespectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters ...
Background: This study aimed to compare efficacy and safety of test-adalimumab (CinnoRA�®, CinnaGen, Iran) to\nthe innovator product (Humira�®, AbbVie, USA) in adult patients with active rheumatoid arthritis (RA).\nMethods: In this randomized, double-blind, active-controlled, non-inferiority trial, a total of 136 patients with\nactive RA were randomized to receive 40 mg subcutaneous injections of either CinnoRA�® or Humira�® every\nother week, while receiving methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day)\nover a period of 24 weeks. Physical examinations, vital sign evaluations, and laboratory tests were conducted\nin patients at baseline and at 12-week and 24-week visits. The primary endpoint in this study was the\nproportion of patients achieving moderate and good disease activity score in 28 joints-erythrocyte\nsedimentation rate (DAS28-ESR)-based European League Against Rheumatism (EULAR) response. The secondary\nendpoints were the proportion of patients achieving American College of Rheumatology (ACR) criteria for\n20% (ACR20), 50% (ACR50), and 70% (ACR70) responses along with the disability index of health assessment\nquestionnaire (HAQ), and safety. Results: Patients who were randomized to CinnoRA�® or Humira�® arms had comparable demographic information,\nlaboratory results, and disease characteristics at baseline. The proportion of patients achieving good and moderate\nEULAR responses in the CinnoRA�® group was non-inferior to the Humira�® group at 12 and 24 weeks based on both\nintention-to-treat (ITT) and per-protocol (PP) populations (all p values >0.05). No significant difference was noted in\nthe proportion of patients attaining ACR20, ACR50, and ACR70 responses in the CinnoRA�® and Humira�® groups\n(all p values >0.05). Further, the difference in HAQ scores and safety outcome measures between treatment\narms was not statistically significant.\nConclusion: CinnoRA�® was shown to be non-inferior to Humira�® in terms of efficacy at week 24 with a\ncomparable safety profile to the reference product....
Background: Hypertension is one of the leading causes of morbidity and mortality in Ethiopia. Treatment usually\ninvolves lifelong medication use. Enalapril is a common drug for the treatment of hypertension in Ethiopia. However,\nthe drug is expensive and, therefore, there is limited capacity for people to afford the treatment. Locally produced\nEnalapril is a cost-effective solution to treat the disease. However, as local medicines regulation does not include\nbioequivalence tests on locally produced drugs, physicians and patients need assurance about the effectiveness\nand safety of local generics. Evidence on therapeutic equivalence is needed on these untested local drugs.\nMethods: This is a hospital-based, randomized, partially blinded, three-cycle crossover trial in single patients,\ncomparing a locally produced version of enalapril with enalapril imported from Europe. Patients involved in this\ntrial are not blinded, as there is no local facility to produce relatively small numbers of placebos or encapsulated\ndrugs. To ensure blinding of study investigators and data analysts, study medications are prepared by an independent\npharmacy unit using opaque medication packaging. The importance of maintaining blinding is also part of patient\npre-trial education. Each N-of-1 trial will consist of three successive 14-day treatment pairs, each pair comprising\n7 days of 5ââ?¬â??20 mg local and 7 days of 5ââ?¬â??20 mg imported enalapril taken once daily in the morning. The primary\noutcome will be the average difference in systolic blood pressure as measured by home blood pressure measurements.\nDiscussion: The number of locally produced products, such as enalapril, being approved without proof of\nbioequivalence is dramatically increasing. By bridging the information gap on bioequivalence, the trial will give\nrigorous evidence on therapeutic equivalence of locally produced enalapril in the treatment of hypertension. If\nthere is no difference, the hypothesized result, then patients can take the local medicine with confidence. This trial will\nalso will determine whether aggregated N-of-1 studies are feasible to evaluate untested generic drugs in resourcelimited\ncountries where bioequivalence testing centers are unavailable....
Monoclonal antibody (mAb)-based therapeutics are playing\nan increasingly important role in the treatment or prevention\nof many important diseases such as cancers,\nautoimmune disorders, and infectious diseases. Multidomain\nmAbs are far more complex than small molecule\ndrugs with intrinsic heterogeneities. The critical quality\nattributes of a given mAb, including structure, post-translational\nmodifications, and functions at biomolecular and\ncellular levels, need to be defined and profiled in details\nduring the developmental phases of a biologics. These\ncritical quality attributes, outlined in this review, serve an\nimportant database for defining the drug properties during\ncommercial production phase aswell as post licensure life\ncycle management. Specially, the molecular characterization,\nfunctional assessment, and effector function analysis\nof mAbs, are reviewed with respect to the critical parameters\nand the methods used for obtaining them. The three\ngroups of analytical methods are three essential and integral\nfacets making up the whole analytical package for a\nmAb-based drug.Such a package is critically important for\nthe licensure andthepost-licensure lifecyclemanagement\nof a therapeutic or prophylactic biologics. In addition, the\nbasic principles on the evaluation of biosimilarmAbswere\ndiscussed briefly based on the recommendations by the\nWorld Health Organization....
Our objective was to evaluate the immunogenicity of branded and biosimilar infliximab\nby detecting changes in T-helper-9 (Th9) percentages induced by an in vitro stimulation test.\nMethods: Peripheral blood mononuclear cells collected from 55 consecutive rheumatoid arthritis\n(RA) outpatients (15 drug free, 20 successfully treated with branded infliximab, 20 branded\ninfliximab inadequate responders) and 10 healthy controls were cultured, with or without 50 Ã?¼g/mL\nof infliximab originator (RemicadeÃ?®) or 50 Ã?¼g/mL of infliximab biosimilar (RemsimaÃ?®) for 18 h.\nTh9 lymphocytes were identified by means of flow cytometry as PU.1 and IRF4-expressing,\nIL-9-secreting CD4+ T cells. Furthermore, the markers CCR7 and CD45RA were used to\ndistinguish naÃ?¯ve from memory IL-9 producer cells. Results: Under unstimulated conditions,\nthe drug-free RA patients had the highest percentages of Th9 lymphocytes. Following stimulation\nwith branded infliximab, the percentages of PU.1 and IRF4-expressing Th9 cells, CCR7+, CD45RAâË?â??\n(central memory) and CCR7âË?â??, CD45RAâË?â?? (effector memory) cells significantly increased in the group\nof inadequate responders, but no significant variation was observed after exposure to the biosimilar\nof infliximab. Conclusions: Th9 cells seem to be involved in the immune response to the epitopes of\nbranded, but not biosimilar, infliximab, and this may depend on the recall and stimulation of both\ncentral and effector memory cells....
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