The rapidly growing and increasingly effective use of Monoclonal Antibodies (mAbs) and other biotherapeutics in the treatment of neoplastic, autoimmune, and inflammatory diseases is an exciting development. Biotherapeutic formulations are significantly more complicated than small molecule drug formulations, contributing to high development and manufacturing costs. Because biotherapeutic proteins are large, structurally complicated, and somewhat fragile molecules (i.e., compared to small molecule drugs) they often require the inclusion of functional excipients in order to ameliorate undesirable properties such as aggregation or short shelf life, or allow for increased concentration permitting smaller administration volumes and reduced administration times. Biotherapeutic proteins can also be affected by differences in the manufacturing process and efficacy can be affected by differences in formulations.
{"title":"Circumventing Polysorbate Induced Unwanted Immunogenicity and Anaphylaxis","authors":"Maggio Et","doi":"10.4172/JBB.1000352","DOIUrl":"https://doi.org/10.4172/JBB.1000352","url":null,"abstract":"The rapidly growing and increasingly effective use of Monoclonal Antibodies (mAbs) and other biotherapeutics in the treatment of neoplastic, autoimmune, and inflammatory diseases is an exciting development. Biotherapeutic formulations are significantly more complicated than small molecule drug formulations, contributing to high development and manufacturing costs. Because biotherapeutic proteins are large, structurally complicated, and somewhat fragile molecules (i.e., compared to small molecule drugs) they often require the inclusion of functional excipients in order to ameliorate undesirable properties such as aggregation or short shelf life, or allow for increased concentration permitting smaller administration volumes and reduced administration times. Biotherapeutic proteins can also be affected by differences in the manufacturing process and efficacy can be affected by differences in formulations.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"17 5 1","pages":"499-500"},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89171595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is known that the decrease of Na+ gradients on cell membrane is a common consequence of cell pathology. According to the classical membrane theory, low permeability of cell membrane for Na+ and high permeability for K+ are the main reasons for asymmetric distribution of inorganic ions between intraand extra-cellular mediums and generation of Membrane Potential (MP) [1]. However, this theory is unable to explain the mechanism of the metabolic control of semi-permeable properties of cell membrane for inorganic ions, which are disturbed in cell pathology. Our previous work, performed on squid axons and snail neurons, has shown that water efflux from the cells has inactivation effect on inward Na+ and Ca2+ currents and activation effect on outward K+ currents, while the water uptake has opposite effect on them [2].
{"title":"Lipid Fluidity as an Essential Therapeutic Tool for Cell Pathology","authors":"S. Ayrapetyan","doi":"10.4172/JBB.10000E80","DOIUrl":"https://doi.org/10.4172/JBB.10000E80","url":null,"abstract":"It is known that the decrease of Na+ gradients on cell membrane is a common consequence of cell pathology. According to the classical membrane theory, low permeability of cell membrane for Na+ and high permeability for K+ are the main reasons for asymmetric distribution of inorganic ions between intraand extra-cellular mediums and generation of Membrane Potential (MP) [1]. However, this theory is unable to explain the mechanism of the metabolic control of semi-permeable properties of cell membrane for inorganic ions, which are disturbed in cell pathology. Our previous work, performed on squid axons and snail neurons, has shown that water efflux from the cells has inactivation effect on inward Na+ and Ca2+ currents and activation effect on outward K+ currents, while the water uptake has opposite effect on them [2].","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"8 1","pages":"0-1"},"PeriodicalIF":0.0,"publicationDate":"2017-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85679230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Present research is intended to develop the Ketorolac Tromethamine (KTM) effervescent floating mini-tablets using compression coating method. Mini-tablets have the advantages of both tablets and multiparticulate formulations such as pellets. The main principle of floating mini-tablets can be applied to decrease the irritant effect of KTM on the stomach by avoiding the direct contact with the gastric mucosa and obtaining a low dosage for prolonged periods. KTM mini-tablets were prepared using 4 mm round flat punches and compression coated with hydroxypropyl methylcellulose and effervescent mixture. The prepared tablets were evaluated for weight variation, thickness, friability, hardness, drug content, in vitro buoyancy and in vitro release and the best formulation was subjected to further in vivo examination. The prepared mini-tablets exhibited satisfactory physicochemical characteristics. Formulation F3 offered the best controlled drug release (99.46 ± 0.93% in 12 h and T80%=9.4 h) along with floating lag time 12 h. Pharmacokinetic studies of F3 formulation in male albino rabbits showed 2.25-fold higher bioavailability and 1.35-fold higher Cmax compared to immediate release core mini-tablets. Hence development of KTM effervescent compression-coated floating mini-tablets is the best way to give through oral route to maximize the therapy.
本研究拟采用压缩包衣法制备酮咯酸Tromethamine (KTM)泡腾型漂浮微型片。迷你片剂具有片剂和多颗粒制剂(如颗粒)的优点。利用漂浮迷你片的主要原理，可以避免直接接触胃粘膜，并获得较长时间的低剂量，以减少KTM对胃的刺激作用。采用4 mm圆扁冲孔，羟丙基甲基纤维素和泡腾液包被，制备KTM微型片剂。对制备的片剂进行重量变化、厚度、脆性、硬度、药物含量、体外浮力、体外释放度等评价，并对最佳处方进行体内检验。制备的迷你片具有良好的理化特性。F3的控释时间为12 h(99.46±0.93%)和9.4 h (T80%=9.4 h)，浮滞时间为12 h。F3在雄性白化病兔体内的药动学研究表明，与速释型核心微型片剂相比，F3的生物利用度和Cmax分别提高了2.25倍和1.35倍。因此，开发KTM泡腾压缩包被微型漂浮片是口服给药的最佳途径，以最大限度地提高治疗效果。
{"title":"Formulation and Pharmacokinetics of Ketorolac Tromethamine Floating Compression Coated Mini-Tablets","authors":"Vemula Sk, Venisetty Rk, Veerareddy Pr","doi":"10.4172/JBB.1000351","DOIUrl":"https://doi.org/10.4172/JBB.1000351","url":null,"abstract":"Present research is intended to develop the Ketorolac Tromethamine (KTM) effervescent floating mini-tablets using compression coating method. Mini-tablets have the advantages of both tablets and multiparticulate formulations such as pellets. The main principle of floating mini-tablets can be applied to decrease the irritant effect of KTM on the stomach by avoiding the direct contact with the gastric mucosa and obtaining a low dosage for prolonged periods. KTM mini-tablets were prepared using 4 mm round flat punches and compression coated with hydroxypropyl methylcellulose and effervescent mixture. The prepared tablets were evaluated for weight variation, thickness, friability, hardness, drug content, in vitro buoyancy and in vitro release and the best formulation was subjected to further in vivo examination. The prepared mini-tablets exhibited satisfactory physicochemical characteristics. Formulation F3 offered the best controlled drug release (99.46 ± 0.93% in 12 h and T80%=9.4 h) along with floating lag time 12 h. Pharmacokinetic studies of F3 formulation in male albino rabbits showed 2.25-fold higher bioavailability and 1.35-fold higher Cmax compared to immediate release core mini-tablets. Hence development of KTM effervescent compression-coated floating mini-tablets is the best way to give through oral route to maximize the therapy.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"60 1","pages":"493-498"},"PeriodicalIF":0.0,"publicationDate":"2017-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89404028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioequivalence studies are evidence of generic drugs quality, demonstrating that the rate and quantity of effective substance absorbed from each of the studied formulations, showed no significant differences. The aim of the pharmacokinetic study of the two formulations, containing 600 mg of Oxcarbazepine, is to analyse bioavailability between the Test Product (Oxicodal® from Synthesis Laboratory S.A.S, Colombia) and the Reference Product (Trileptal® from Novartis Laboratory) and to affirm the Bioequivalence. Therefore, a study was developed in 24 healthy volunteers; an open, four periods and four randomized sequences, with one dose of 600 mg during fasting and postprandial conditions, and 7-day wash time between each period study. Conducting the study in 4 periods obeys the need to know if there are differences in relation to the presence or not of food during the bioavailability of the formulations studied. The benefits sought in this study are to offer public health a guarantee of quality, safety and inter-changeability of the drugs studied to increase the population's access to generic medicines. The analytical method used was HPLC chromatography UV detector. The 90% confidence interval for the parameters Cmax, AUC0-t and AUC0-∞, according to European guidelines and the FDA is within the permitted ranges for the declaration of bioequivalence and compatibility of the Synthesis S.A.S (Colombia) product Oxicodal®, with the Novartis Laboratories Reference Product Trileptal®, for both feeding conditions, fasting and postprandial.
{"title":"600 mg Oxcarbazepine Tablets Bioequivalence Study","authors":"M. Vargas, Villarraga Ea","doi":"10.4172/JBB.1000350","DOIUrl":"https://doi.org/10.4172/JBB.1000350","url":null,"abstract":"Bioequivalence studies are evidence of generic drugs quality, demonstrating that the rate and quantity of effective substance absorbed from each of the studied formulations, showed no significant differences. The aim of the pharmacokinetic study of the two formulations, containing 600 mg of Oxcarbazepine, is to analyse bioavailability between the Test Product (Oxicodal® from Synthesis Laboratory S.A.S, Colombia) and the Reference Product (Trileptal® from Novartis Laboratory) and to affirm the Bioequivalence. Therefore, a study was developed in 24 healthy volunteers; an open, four periods and four randomized sequences, with one dose of 600 mg during fasting and postprandial conditions, and 7-day wash time between each period study. Conducting the study in 4 periods obeys the need to know if there are differences in relation to the presence or not of food during the bioavailability of the formulations studied. The benefits sought in this study are to offer public health a guarantee of quality, safety and inter-changeability of the drugs studied to increase the population's access to generic medicines. \u0000 \u0000The analytical method used was HPLC chromatography UV detector. The 90% confidence interval for the parameters Cmax, AUC0-t and AUC0-∞, according to European guidelines and the FDA is within the permitted ranges for the declaration of bioequivalence and compatibility of the Synthesis S.A.S (Colombia) product Oxicodal®, with the Novartis Laboratories Reference Product Trileptal®, for both feeding conditions, fasting and postprandial.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"77 1","pages":"489-492"},"PeriodicalIF":0.0,"publicationDate":"2017-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76776206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A study with the aim to compare the bioavailability of two 400 mg imatinib formulations, test product Zeite® from Laboratorio Synthesis S.A.S., Colombia, and reference product Glivec® from Novartis Pharma, and determine if bioequivalence can be declared, was runned. It was an open, four periods and two pre-randomized sequences, crossed study, with a 400mg single dose in fastened and fed conditions, in 30 healthy Colombian volunteers; wash time was 7 days in between periods, with sampling between 0 and 72 hours after drug administration, which was randomly administered in each period. The analytical method used was high performance liquid chromatography with ultraviolet detector, HPLC UV for plasma identification and quantification of imatinib. The confidence interval of 90% of parameters Cmax, AUCall and AUC0-Inf, were taken to statistical analysis and were found, according to the european guidelines for research, which allowed to declare bioequivalence and interchangeability between the products from Laboratorios Synthesis S.A.S. and the reference product from Laboratory Novartis Pharma
{"title":"Bioequivalence Study of Imatinib Formulations that Contain 400 mg in Healthy Colombians","authors":"M. Vargas, E. Villarraga","doi":"10.4172/JBB.1000349","DOIUrl":"https://doi.org/10.4172/JBB.1000349","url":null,"abstract":"A study with the aim to compare the bioavailability of two 400 mg imatinib formulations, test product Zeite® from Laboratorio Synthesis S.A.S., Colombia, and reference product Glivec® from Novartis Pharma, and determine if bioequivalence can be declared, was runned. It was an open, four periods and two pre-randomized sequences, crossed study, with a 400mg single dose in fastened and fed conditions, in 30 healthy Colombian volunteers; wash time was 7 days in between periods, with sampling between 0 and 72 hours after drug administration, which was randomly administered in each period. The analytical method used was high performance liquid chromatography with ultraviolet detector, HPLC UV for plasma identification and quantification of imatinib. The confidence interval of 90% of parameters Cmax, AUCall and AUC0-Inf, were taken to statistical analysis and were found, according to the european guidelines for research, which allowed to declare bioequivalence and interchangeability between the products from Laboratorios Synthesis S.A.S. and the reference product from Laboratory Novartis Pharma","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"67 1","pages":"484-488"},"PeriodicalIF":0.0,"publicationDate":"2017-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73801291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dolores Rc, Antunes Nj, Moreno R, Di Vaio P, Magli E, De Nucci G
Introduction: Low-dose acetylsalicylic acid is used as antithrombotic agent and the enteric-coated formulations are widely used to minimize the gastrointestinal side effects. Aim: To compare the bioavailability of two acetylsalicylic acid formulations (Ecasil-81®, 81 mg coated tablet) in fasting healthy volunteers. Methods: Healthy volunteers (n=16) were recruited to a monocentric, open label, randomized, two-way crossover pharmacokinetic study, with seven days washout period between the treatments. They received a single 81 mg oral dose of a test (new formulation) or a standard reference formulation of acetylsalicylic acid (Ecasil-81®) after about 8 h fasting. Blood samples were collected over a period of 36 h. The salicylic acid plasma concentration was evaluated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Noncompartmental pharmacokinetic analysis was performed using the WinNonlin program. Results: The maximum plasma concentration (Cmax) of salicylic acid was 5433 and 5719 ng/mL reached in 3.66 and 4.02 h (tmax) for the test and the reference formulation, respectively. The 90% confidence interval of the ratios of geometric means of Cmax and area under curve of plasma concentration until the last concentration observed (AUC0- last) were within the interval 80-125%. Conclusion: The new acetylsalicylic acid formulation has a bioavailability equivalent to the reference formulation for the rate and the extent of absorption.
{"title":"Comparative Bioavailability Study of Two 81 mg Coated Tablet Formulations of Acetylsalicylic Acid in Fasting Healthy Volunteers","authors":"Dolores Rc, Antunes Nj, Moreno R, Di Vaio P, Magli E, De Nucci G","doi":"10.4172/JBB.1000348","DOIUrl":"https://doi.org/10.4172/JBB.1000348","url":null,"abstract":"Introduction: Low-dose acetylsalicylic acid is used as antithrombotic agent and the enteric-coated formulations are widely used to minimize the gastrointestinal side effects. \u0000Aim: To compare the bioavailability of two acetylsalicylic acid formulations (Ecasil-81®, 81 mg coated tablet) in fasting healthy volunteers. \u0000Methods: Healthy volunteers (n=16) were recruited to a monocentric, open label, randomized, two-way crossover pharmacokinetic study, with seven days washout period between the treatments. They received a single 81 mg oral dose of a test (new formulation) or a standard reference formulation of acetylsalicylic acid (Ecasil-81®) after about 8 h fasting. Blood samples were collected over a period of 36 h. The salicylic acid plasma concentration was evaluated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Noncompartmental pharmacokinetic analysis was performed using the WinNonlin program. \u0000Results: The maximum plasma concentration (Cmax) of salicylic acid was 5433 and 5719 ng/mL reached in 3.66 and 4.02 h (tmax) for the test and the reference formulation, respectively. The 90% confidence interval of the ratios of geometric means of Cmax and area under curve of plasma concentration until the last concentration observed (AUC0- last) were within the interval 80-125%. \u0000Conclusion: The new acetylsalicylic acid formulation has a bioavailability equivalent to the reference formulation for the rate and the extent of absorption.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"45 1","pages":"477-483"},"PeriodicalIF":0.0,"publicationDate":"2017-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86973244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali H, Alvi A, Fatima S, Zafar F, Naveed S, Khan K, Ali U, Tariq A, Naqvi Gr, Mallick N
Dengue a majorly imperative arthropod-borne infection of viral origin has stroked the humans Worldwide. It has been estimated that about 2.5 billion inhabitants are at threatened by this infection around the globe. Dengue fever has become pandemic-prone viral disease prevailing all over subtropical and tropical regions. Majorly four characteristics of closely related serotypes of dengue are DENV-1, DENV-2, DENV-3 and DENV-4. Dengue fevers pass on by the bite of an infected female Aedes aegypti mosquito. The topmost ailments include; internal bleeding, Dengue Hemorrhagic Fever (DHF) which may lead to Circulatory Shock Syndrome (CSS), high temperature, cold like illness, urticaria, severe joint pain, thrombocytopenia and heme-concentration. From the recent years, this "break-bone fever" has become out breaking viral disease in Pakistan because Urbanization provided the ideal environment for these mosquitoes which includes presence of stagnant water in indoor drainage holes, contaminated water for drinking, poverty, immune compromised individuals and insufficient medical facilities. Such causative factors embrace viral disease that brings about high rate of mortality and morbidity. But nowadays, rational prescribing and the facilities provided by pharmaceutical care has become necessary element of health care for achieving definite outcomes that can improve a patient's quality of life.
{"title":"Dengue Fever in Pakistan, Episodes of Epidemic to Endemic: Treatment Challenges, Prevention and Current Facts","authors":"Ali H, Alvi A, Fatima S, Zafar F, Naveed S, Khan K, Ali U, Tariq A, Naqvi Gr, Mallick N","doi":"10.4172/JBB.1000347","DOIUrl":"https://doi.org/10.4172/JBB.1000347","url":null,"abstract":"Dengue a majorly imperative arthropod-borne infection of viral origin has stroked the humans Worldwide. It has been estimated that about 2.5 billion inhabitants are at threatened by this infection around the globe. Dengue fever has become pandemic-prone viral disease prevailing all over subtropical and tropical regions. Majorly four characteristics of closely related serotypes of dengue are DENV-1, DENV-2, DENV-3 and DENV-4. Dengue fevers pass on by the bite of an infected female Aedes aegypti mosquito. The topmost ailments include; internal bleeding, Dengue Hemorrhagic Fever (DHF) which may lead to Circulatory Shock Syndrome (CSS), high temperature, cold like illness, urticaria, severe joint pain, thrombocytopenia and heme-concentration. From the recent years, this \"break-bone fever\" has become out breaking viral disease in Pakistan because Urbanization provided the ideal environment for these mosquitoes which includes presence of stagnant water in indoor drainage holes, contaminated water for drinking, poverty, immune compromised individuals and insufficient medical facilities. Such causative factors embrace viral disease that brings about high rate of mortality and morbidity. But nowadays, rational prescribing and the facilities provided by pharmaceutical care has become necessary element of health care for achieving definite outcomes that can improve a patient's quality of life.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"329 1","pages":"473-476"},"PeriodicalIF":0.0,"publicationDate":"2017-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74064479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Histopathological evidence of extensive fibrosis may produce myocardial areas where fibrous tissue separates the muscle fibers from each other. The dismally connected fibers in infected myocardial tissue with continuous fibro-degenerative modification may induce anomalous electrophysiological characteristics. Electrical coupling between adjacent fibers is difficult to occur when fibrosis surrounds groups of myocytes [1-4]. The microarchitecture and anisotropic characteristics may play an important role in re-entry by causing inhomogeneous and discontinuous propagation of the impulse. This non-uniform anisotropic property causes an irregular and fractionated propagation of the depolarization wave in the transverse direction [5-8]. Structural inhomogeneity or the common distinction in electrophysiological or ultra-structural properties plays a major role in the induction of re-entrant circuits and malignant arrhythmias due to the elevated probability of unidirectional block of the premature impulse and conduction delay [7-10].
{"title":"Fibrosis-Induced Abnormalities of the Cardiac Conduction System andMalignant Arrhythmias in Patients with Chagas Disease","authors":"Centurión Oa, García Lb","doi":"10.4172/JBB.10000E79","DOIUrl":"https://doi.org/10.4172/JBB.10000E79","url":null,"abstract":"Histopathological evidence of extensive fibrosis may produce myocardial areas where fibrous tissue separates the muscle fibers from each other. The dismally connected fibers in infected myocardial tissue with continuous fibro-degenerative modification may induce anomalous electrophysiological characteristics. Electrical coupling between adjacent fibers is difficult to occur when fibrosis surrounds groups of myocytes [1-4]. The microarchitecture and anisotropic characteristics may play an important role in re-entry by causing inhomogeneous and discontinuous propagation of the impulse. This non-uniform anisotropic property causes an irregular and fractionated propagation of the depolarization wave in the transverse direction [5-8]. Structural inhomogeneity or the common distinction in electrophysiological or ultra-structural properties plays a major role in the induction of re-entrant circuits and malignant arrhythmias due to the elevated probability of unidirectional block of the premature impulse and conduction delay [7-10].","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89722967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Inotai, M. Csanádi, D. Vitezić, I. Francetic, T. Tesar, T. Bochenek, L. Lorenzovici, P. Dylst, Z. Kaló
Biosimilar medicines can generate savings to the society. However, if patient access to original biologic medicines is limited, the main benefit of biosimilar medicines is to treat more patients from the same health care budget and hence generate more health gain. The aim of this policy paper is to provide recommendations on how to maximise the value proposition of biosimilar medicines in lower income countries with more limited health care resources. From the clinical perspective, first line use of multi-source, off-patent biologics should be considered for all treatment naive patients before prescribing any other patented biologic therapies without major added benefit. Systematic literature reviews indicate that significant and quantifiable economic benefits from switching patients on maintenance biologic to biosimilars should not be sacrificed for non-quantifiable and fairly low risks of immunogenicity, hence a single switch of patients from an original biologic to its biosimilar alternative under medical supervision should be mandated after patent expiry. From the health economic perspective authors advocate the use of cost-utility analysis to evaluate the full economic value of biosimilars. In sensitivity analyses decision-makers can explore the level of risk associated with immunogenicity, where switch of patients treated by original biologics is not the preferred policy approach anymore. However, authors still advocate the collection of real world pharmacovigilance data after switching patients to biosimilars, and reassessment of cost-effectiveness ratio after more real-world data becomes available. Appropriateness of biosimilar drug policies is equally important to market access of new biologic therapies in lower income countries.
{"title":"Policy Practices to Maximise Social Benefit from Biosimilars","authors":"A. Inotai, M. Csanádi, D. Vitezić, I. Francetic, T. Tesar, T. Bochenek, L. Lorenzovici, P. Dylst, Z. Kaló","doi":"10.4172/JBB.1000346","DOIUrl":"https://doi.org/10.4172/JBB.1000346","url":null,"abstract":"Biosimilar medicines can generate savings to the society. However, if patient access to original biologic medicines is limited, the main benefit of biosimilar medicines is to treat more patients from the same health care budget and hence generate more health gain. \u0000The aim of this policy paper is to provide recommendations on how to maximise the value proposition of biosimilar medicines in lower income countries with more limited health care resources. \u0000From the clinical perspective, first line use of multi-source, off-patent biologics should be considered for all treatment naive patients before prescribing any other patented biologic therapies without major added benefit. Systematic literature reviews indicate that significant and quantifiable economic benefits from switching patients on maintenance biologic to biosimilars should not be sacrificed for non-quantifiable and fairly low risks of immunogenicity, hence a single switch of patients from an original biologic to its biosimilar alternative under medical supervision should be mandated after patent expiry. \u0000From the health economic perspective authors advocate the use of cost-utility analysis to evaluate the full economic value of biosimilars. In sensitivity analyses decision-makers can explore the level of risk associated with immunogenicity, where switch of patients treated by original biologics is not the preferred policy approach anymore. However, authors still advocate the collection of real world pharmacovigilance data after switching patients to biosimilars, and reassessment of cost-effectiveness ratio after more real-world data becomes available. \u0000Appropriateness of biosimilar drug policies is equally important to market access of new biologic therapies in lower income countries.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"8 1","pages":"467-472"},"PeriodicalIF":0.0,"publicationDate":"2017-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89538332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Adnan, K. Mohammad, Mohammad Emdad Hossain Manik
Statins are 3-Hydroxy-3-methylgutaryl CoA (HMG CoA) reductase inhibitors and mainly used in cardiovascular diseases. However, they are also widely known for their anticancer activities mediated by antiproliferative, proapoptotic, anti-invasive, and radio sensitizing properties. They are tested alone in several clinical trials for their anticancer activity and the response in not satisfactory due to high dose requirements in humans. Tumor inhibitory concentration of statins is 10-100 μM for different cancer cell lines when tested in vitro. But statins can cause anorexia and death in some individuals if concentration is reached to 20-25 μM in serum. So, there is high risk factor. To avoid these unwanted harmful effects, we can give statins in combination with other chemotherapeutic drugs for synergism. It will reduce the concentration of statins in dosage, and can avoid unwanted toxic effects. When used along with the other chemo therapeutic agents like prenylation inhibitors, NSAIDS and standard chemotherapeutic agents, they have shown much better results at lower doses with little or no toxicity.
他汀类药物是3-羟基-3-甲基gutaryl CoA (HMG CoA)还原酶抑制剂，主要用于心血管疾病。然而，它们也因其抗增殖、促凋亡、抗侵袭和放射性致敏特性介导的抗癌活性而广为人知。它们在几个临床试验中单独测试了它们的抗癌活性，但由于对人体的高剂量要求，反应并不令人满意。他汀类药物体外抑瘤浓度为10 ~ 100 μM。但当他汀类药物在血清中的浓度达到20 ~ 25 μM时，可引起部分个体的厌食和死亡。所以，这是一个高风险因素。为了避免这些不必要的有害影响，我们可以将他汀类药物与其他化疗药物联合使用以实现协同作用。它将降低他汀类药物的剂量浓度，并可以避免不必要的毒性作用。当与其他化疗药物一起使用时，如戊酰化抑制剂，非甾体抗炎药和标准化疗药物，它们在低剂量下显示出更好的效果，几乎没有毒性。
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