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Lixivaptan
Lixivaptan (VPA-985) is an orally-active, non-peptide, selective vasopressin 2 receptor antagonist being developed as an investigational drug by Palladio Biosciences, Inc. (Palladio), a subsidiary of Centessa Pharmaceuticals plc. , lixivaptan is in Phase III clinical development for the treatment of Autosomal dominant polycystic kidney disease (ADPKD), the most common form of polycystic kidney disease. The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to lixivaptan for the treatment of ADPKD. Mechanism of action Lixivaptan is a potent, non-peptide, selective vasopressin receptor antagonist. It is a member of the vaptan class of drugs. Hyponatremia V2 receptor antagonists inhibit the binding of arginine vasopressin to vasopressin receptor 2 (V2R) in kidney tubular epithelial cells, thereby having a net effect of aquaresis, or electrolyte free water excretion. This property of vaptans explains their use as therapies to treat euvolemic and hypervol ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vasopressin Receptor Antagonist
A vasopressin receptor antagonist (VRA) is an agent that interferes with action at the vasopressin receptors. Most commonly VRAs are used in the treatment of hyponatremia, especially in patients with congestive heart failure, liver cirrhosis or SIADH. Types Vaptans The "vaptan" drugs act by directly blocking the action of vasopressin at its receptors ( V1A, V1B and V2). These receptors have a variety of functions, with the V1A and V2 receptors are expressed peripherally and involved in the modulation of blood pressure and kidney function respectively, while the V1A and V1B receptors are expressed in the central nervous system. V1A is expressed in many regions of the brain, and has been linked to a variety of social behaviors in humans and animals. The vaptan class of drugs contains a number of compounds with varying selectivity, several of which are either already in clinical use or in clinical trials as of 2009. ;Unselective (mixed V1A/V2) * Conivaptan ;V1A selective (V1RA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vasopressin Receptor Antagonist
A vasopressin receptor antagonist (VRA) is an agent that interferes with action at the vasopressin receptors. Most commonly VRAs are used in the treatment of hyponatremia, especially in patients with congestive heart failure, liver cirrhosis or SIADH. Types Vaptans The "vaptan" drugs act by directly blocking the action of vasopressin at its receptors ( V1A, V1B and V2). These receptors have a variety of functions, with the V1A and V2 receptors are expressed peripherally and involved in the modulation of blood pressure and kidney function respectively, while the V1A and V1B receptors are expressed in the central nervous system. V1A is expressed in many regions of the brain, and has been linked to a variety of social behaviors in humans and animals. The vaptan class of drugs contains a number of compounds with varying selectivity, several of which are either already in clinical use or in clinical trials as of 2009. ;Unselective (mixed V1A/V2) * Conivaptan ;V1A selective (V1RA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Autosomal Dominant Polycystic Kidney Disease
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited human disorders and the most common hereditary kidney disease. It is associated with large interfamilial and intrafamilial variability, which can be explained to a large extent by its genetic heterogeneity and modifier genes. It is also the most common of the inherited cystic kidney diseases — a group of disorders with related but distinct pathogenesis, characterized by the development of renal cysts and various extrarenal manifestations, which in case of ADPKD include cysts in other organs, such as the liver, seminal vesicles, pancreas, and arachnoid membrane, as well as other abnormalities, such as intracranial aneurysms and dolichoectasias, aortic root dilatation and aneurysms, mitral valve prolapse, and abdominal wall hernias. Over 50% of patients with ADPKD eventually develop end stage kidney disease and require dialysis or kidney transplantation.; Reprinted in ADPKD ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Risk Evaluation And Mitigation Strategies
Risk Evaluation and Mitigation Strategies (REMS) is a program of the US Food and Drug Administration for the monitoring of medications with a high potential for serious adverse effects. REMS applies only to specific prescription drugs, but can apply to brand name or generic drugs. The REMS program was formalized in 2007. The FDA determines as part of the drug approvals process that a REMS is necessary, and the drug company develops and maintains the individual program. REMS applies only to specific prescription drugs, but can apply to brand name or generic drugs. REMS for generic drugs may be created in collaboration with the manufacture of the brand name drug. The FDA may remove the REMS requirement if it is found to not improve patient safety. The REMS program developed out of previous systems dating back to the 1980s for monitoring the use of a small number of high-risk drugs such as the Accutane, which causes serious birth defects, Clozaril, which can cause agranulocytosis, a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Open Label
An open-label trial, or open trial, is a type of clinical trial in which information is not withheld from trial participants. In particular, both the researchers and participants know which treatment is being administered. This contrasts with a blinded experiment, double-blinded trial, where information is withheld both from the researchers and the participants to reduce bias. Open-label trials may be appropriate for comparing two similar treatments to determine which is most effective, such as a comparison of different prescription drug, prescription anticoagulants, or possible relief from symptoms of some disorders when a placebo is given. An open-label trial may still be randomized controlled trial, randomized. Open-label trials may also be uncontrolled (without a placebo-controlled study, placebo group), with all participants receiving the same treatment. References {{Medical research studies Design of experiments Clinical trials Scientific method Research methods ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Titration
Titration (also known as titrimetry and volumetric analysis) is a common laboratory method of quantitative chemical analysis to determine the concentration of an identified analyte (a substance to be analyzed). A reagent, termed the ''titrant'' or ''titrator'', is prepared as a standard solution of known concentration and volume. The titrant reacts with a solution of ''analyte'' (which may also be termed the ''titrand'') to determine the analyte's concentration. The volume of titrant that reacted with the analyte is termed the ''titration volume''. History and etymology The word "titration" descends from the French word ''titrer'' (1543), meaning the proportion of gold or silver in coins or in works of gold or silver; i.e., a measure of fineness or purity. ''Tiltre'' became ''titre'', which thus came to mean the "fineness of alloyed gold", and then the "concentration of a substance in a given sample". In 1828, the French chemist Joseph Louis Gay-Lussac first used ''titre'' as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phase III Study
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over seve ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Double-blind
In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. In some cases, while blinding would be useful, it is impossible or unethical. For example, it is not possible to blind a patient to their treatment in a physical therapy intervention. A good clinical protocol ensures that blinding is as effective as possible within ethical and practical constraints. During the course of an experiment, a participant becomes unblinded if they deduce or otherwise obtain information that has been masked to them. For example, a patient who experiences a side effect may correc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phase III Clinical Trial
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over sever ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Estimated Glomerular Filtration Rate
Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D. One of the measures of kidney function is the glomerular filtration rate (GFR). Glomerular filtration rate describes the flow rate of filtered fluid through the kidney. Creatinine clearance rate (CCr or CrCl) is the volume of blood plasma that is cleared of creatinine per unit time and is a useful measure for approximating the GFR. Creatinine clearance exceeds GFR due to creatinine secretion, which can be blocked by cimetidine. Both GFR and CCr may be accurately calculated by comparative measurements of substances in the blood and urine, or estimated by formulas using just a blood test result (eGFR and eCCr) The results of these tests are used ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Urine Osmolality
Urine osmolality is a measure of urine concentration, in which large values indicate concentrated urine and small values indicate diluted urine. Consumption of water (including water contained in food) affects the osmolality of urine. Osmolality is measured by osmometer, which evaluates the freezing point depression of a solution and supplies results as milliosmoles per kilogram of water while specific gravity is measured by colorimetric strips, refractometer, hydrometer and pyknometer. In healthy humans with restricted fluid intake, urine osmolality should be greater than 800 Osmole (unit), mOsm/kg, while a 24-hour urine osmolality should average between 500 and 800 mOsm/kg. Urine osmolality in humans can range from approximately 50 to 1200 mOsm/kg, depending on whether the person has recently drunk a large quantity of water (the lower number) or has gone without water for a long time (the higher number). Plasma osmolality with typical fluid intake often averages approximately ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pharmacodynamic
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for example, infection). Pharmacodynamics and pharmacokinetics are the main branches of pharmacology, being itself a topic of biology interested in the study of the interactions between both endogenous and exogenous chemical substances with living organisms. In particular, pharmacodynamics is the study of how a drug affects an organism, whereas pharmacokinetics is the study of how the organism affects the drug. Both together influence dosing, benefit, and adverse effects. Pharmacodynamics is sometimes abbreviated as PD and pharmacokinetics as PK, especially in combined reference (for example, when speaking of PK/PD models). Pharmacodynamics places particular emphasis on dose–response relationships, that is, the relationships between drug ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
