New Drug Approvals

Home » Posts tagged 'manufacturing' (Page 14)

Tag Archives: manufacturing

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Blog Stats

  • 4,862,777 hits

Flag and hits

Flag Counter

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 37.8K other subscribers
Follow New Drug Approvals on WordPress.com

Archives

Categories

Recent Posts

Flag Counter

ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 37.8K other subscribers
DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

Verified Services

View Full Profile →

Archives

Categories

Flag Counter

AstraZeneca buys Pearl Therapeutics in $1.15bn deal


obstructive pulmonary disease

The UK’s second largest drug company, AstraZeneca, has announced that it will buy US-based lung disease drug specialist Pearl Therapeutics in a deal worth up to $1.15bn (£742m).

seagullread all at

http://www.pharmaceutical-technology.com/news/newsastrazeneca-buys-pearl-therapeutics-in-115bn-deal?WT.mc_id=DN_News

Vitaros Approved in 10 Countries


Vitaros, alprostadil

7-[(1R,3R)-3-hydroxy-2-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid

Apricus Biosciences Inc. said that its impotence drug Vitaros has been approved in 10 European countries. The company said Vitaros is now approved in the Netherlands, Germany, France, Italy, and the U.K., among other countries, for the treatment of erectile dysfunction.

The active ingredient in Vitaros, alprostadil, is an ingredient in other approved impotence treatments and Apricus is also studying it as a treatment for female sexual arousal disorder.

http://www.dddmag.com/news/2013/06/vitaros-approved-10-countries?et_cid=3306519&et_rid=523035093&type=headline

Prostaglandin E1 (PGE1), known pharmaceutically as alprostadil,[1] is a prostaglandin. It is a drug used in the treatment of erectile dysfunction[2] and has vasodilatory properties.

Patent ductus arteriosus

Alprostadil is also used in maintaining a patent ductus arteriosus in newborns. This is primarily useful when there is threat of premature closure of the ductus arteriosus in an infant with ductal-dependent congenital heart disease, including cyanotic lesions (e.g., pulmonary atresia/stenosis, tricuspid atresia/stenosis, transposition of the great arteries) and acyanotic lesions (e.g., coarctation of the aorta, hypoplastic left heart syndrome, critical aortic stenosis, interrupted aortic arch).

Sexual dysfunction

Alprostadil is sold in the United States as urethral suppositories and in injectable form. The suppositories are sold under the brand name MUSE.[3] The injectable forms are Edex[4] and Caverject.[5] Muse delivers alprostadil as a penile suppository, inserted into the urethra, at least ten minutes before the erection will be needed. Caverject and Edex are similarly fast-acting, but instead are injected by syringe directly into the corpus cavernosum of the penis.

Apricus Biosciences is developing proprietary drugs; Vitaros for men with erectile dysfunction, Femprox for female sexual arousal disorder and RayVa for Raynaud’s phenomenon. Two Phase III studies have been completed for Vitaros, and approval has been granted in Canada. Apricus Biosciences is seeking regulatory approval in Europe, South America, and other territories. Apricus Biosciences sold the rights for Vitaros in the US to Warner Chilcott.[6]

Alprostadil is also available as a generic. The major cost is that it must be mixed by a compounding pharmacy and supplies of alprostadil may be difficult to obtain. There are different formulations, including Bimix and Trimix, which may include papaverine and/or phentolamine. A typical mix might be 30 mg of papaverine, 2 mg of phentolamine, and 20 mcg alprostadil. As a generic, it is much less expensive than the pre-packaged injectables. It is premixed and must be kept refrigerated and the user must load a syringe with the quantity needed.

Critical limb ischemia

Alprostadil is also used for critical limb ischemia. It increases blood flow by peripheral vasodilation within 5 minutes and induces angiogenesis. It is most effective when the ankle pressure is at least 30 mmHg and at least one tibial artery is patent.

  1.  Cawello W, Leonhardt A, Schweer H, Seyberth HW, Bonn R, Lomeli AL (September 1995). “Dose proportional pharmacokinetics of alprostadil (prostaglandin E1) in healthy volunteers following intravenous infusion”. British Journal of Clinical Pharmacology 40 (3): 273–6. PMC 1365109. PMID 8527291.
  2.  Harding LM, Adeniyi A, Everson R, Barker S, Ralph DJ, Baranowski AP (December 2002). “Comparison of a needle-free high-pressure injection system with needle-tipped injection of intracavernosal alprostadil for erectile dysfunction”. International Journal of Impotence Research 14 (6): 498–501. doi:10.1038/sj.ijir.3900916. PMID 12494285.
  3.  “Muse Suppository – Facts and Comparisons”. Drugs.com. Retrieved 4 January 2013.
  4.  Edex – Facts and Comparisons Drugs.com
  5.  Caverject – Facts and Comparisons Drugs.com
  6.  Fain Hughes (2007-10-29). “NEXM: Dutton Sees Strong Speculative Buy and 12-Month Price Double”. Retrieved 2007-11-01.

Prostaglandin E1 (alprostadil, PGE1) erectile dysfunction drug, molecular model. PGE1 is a prostaglandin used in the treatment of erectile dysfunction. Stock Photo - 17817688
Prostaglandin E1 (alprostadil, PGE1) erectile dysfunction drug, molecular model. PGE1 is a prostaglandin used in the treatment of erectile dysfunction.

Study Finds Substances from African Medicinal Plants Could Help Stop Tumour Growth


 

 

Sections of the root of the giant globe thistle.

photo: Victor Kuete, Institute of Pharmaceutical Sciences and Biochemistry

http://scicasts.com/cancer/6122-study-finds-substances-from-african-medicinal-plants-could-help-stop-tumour-growth

African medicinal plants contain chemicals that may be able to stop the spread of cancer cells. This is the conclusion of researchers following laboratory experiments conducted at Johannes Gutenberg University Mainz (JGU). The plant materials will now undergo further analysis in order to evaluate their therapeutic potential.

“The active substances present in African medicinal plants may be capable of killing off tumour cells that are resistant to more than one drug. They thus represent an excellent starting point for the development of new therapeutic treatments for cancers that do not respond to conventional chemotherapy regimens,” explained Professor Thomas Efferth of the Institute of Pharmaceutical Sciences and Biochemistry – Therapeutic Life Sciences at Mainz University. For the past four years, Efferth and biochemist Dr. Victor Keute of the University of Dschang in Cameroon have been studying the active substances in African plants such as the giant globe thistle, wild pepper, speargrass, and Ethiopian pepper.

http://scicasts.com/cancer/6122-study-finds-substances-from-african-medicinal-plants-could-help-stop-tumour-growth

Krill oil is being studied as a natural remedy for high cholesterol


Krill Oil

Krill are shrimp-like crustaceans that are approximately 1 to 6 centimeters long. They live is the ocean, where they feed mainly on phytoplankton. They’re near the bottom of the food chain and are eaten by whales, seals, penguins, squid and fish.

Commercial fishing of krill occurs primarily in the Southern Ocean and the northern Pacific Ocean along the coasts of Canada and Japan. Krill that are caught are used for aquaculture and aquarium feeds, sport fishing bait or they are eaten as food. In Japan, krill that’s caught for food is called okiami.

Krill oil, the oil that’s found naturally in krill, is extracted and sold as a nutritional supplement. It’s sold in some health food stores and online in capsule form.

Krill oil contains omega-3 fatty acids, which is the main reason it’s becoming popular as a nutritional supplement.

Another reason krill oil is becoming popular is because it contains an antioxidant called astaxanthin. The algae that krill eat produces the bright red pigment astaxanthin that gives krill and other crustaceans such as lobster and shrimp their reddish-pink color.

Antioxidants protect our body cells from damage from free radicals, unstable substances that are thought to contribute to certain chronic diseases. Unlike many other antioxidants, astaxanthin crosses the blood-brain barrier, where it could theoretically protect the eye, brain and central nervous system from free radical damage.

The recent popularity of krill oil supplements has raised concerns that it could threaten the population of its predators, including penguins, seals and whales. people use krill oil for the same reasons they use fish oil, flax oil or other omega-3 fatty acids. Unlike fish oil, krill oil doesn’t cause fishy burps or an aftertaste, a common side effect of fish oil. Also, krill oil contains higher amounts of astaxanthin than fish oil. Here are some specific conditions for which it’s used.

1) High Cholesterol

Krill oil is being studied as a natural remedy for high cholesterol. In one study, 120 people were given krill oil, fish oil or a placebo. Krill oil reduced LDL (commonly referred to as “bad”) cholesterol by 34% and increased HDL (“good”) cholesterol by 43.5% compared to the placebo. In comparison, fish oil reduced LDL cholesterol by 4.6% and increased HDL cholesterol by 4.2%. Krill also lowered triglycerides.

2) Premenstrual Syndrome

Preliminary research suggests krill oil may help reduce symptoms of premenstrual syndrome (PMS), however, more research is needed.

Arthritis

A study in the Journal of the American College of Nutrition examined krill oil (300 mg daily) compared to a placebo and found that krill oil was effective at reducing arthritis symptoms and inflammation.

People with allergies to seafood shouldn’t use krill oil. People with bleeding disorders shouldn’t use krill oil unless under the supervision of a qualified health professional.

Side effects of krill oil may include loose stools, diarrhea or indigestion.

people taking blood thinners (anticoagulant or anti-platelet medication), such as aspirin, warfarin (Coumadin), heparin, clopidogrel (Plavix), non-steroidal anti-inflammatory medications (NSAIDS) such as ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve) should only use krill oil under a physician’s supervision.

Krill oil should also be used with caution by people taking herbs and supplements that are thought to increase the risk of bleeding, such as ginkgo biloba and garlic.

Sources

Bunea R, El Farrah K, Deutsch L.Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia. Altern Med Rev. (2004) 9.4: 420-428.

Deutsch L. Evaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptoms. J Am Coll Nutr. (2007) 26.1: 39-48.

MORE INFO

Krill oil is a nutrient from a tiny crustacean (similar to a shrimp) that lives in the icy waters around the Antarctic. It is a rich source of the omega-3 essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

The main selling points for krill oil are that its omega-3s are packaged differently from fish oils, in the form of a phospholipid that is easier for the body to absorb. This better absorption rate – up to 60 per cent, according to some manufacturers – means less capsules need to be taken to achieve the desired health benefits.

It is also said to have the added bonus of containing another essential nutrient, choline, as well as an antioxidant, astaxanthin. Astaxanthin is found in sea algae and it’s what gives shrimp, lobster, salmon, krill and other sea-life that feed on algae their rosy color.

Krill oil supplements are also more expensive than fish oils because of the extensive processes undertaken to ensure quality and eco-sustainability. However, many argue that it is better value for money, as you have to take less capsules than if you were taking fish oil.

A positive genotoxicity result can throw the fate of a promising drug candidate—in which a firm has invested significant time and money—into doubt


A positive genotoxicity result can throw the fate of a promising drug candidate-in which a firm has invested significant time and money-into doubt. The statistical improbability and challenges of bringing a drug to market become paramount.

READ ALL AT

http://www.dddmag.com/articles/2013/06/following-genotoxicity?et_cid=3304624&et_rid=523035093&location=top

 

 

BY WORLD DRUG TRACKER

Automating Lead Optimization


This diagram illustrates the methods used to determine solubility as a compound advances toward further clinical study, and the increasing reach of automation and informatics systems. Initially, screens are run in silico on a library after hits are determined through a high-throughput screen; then various kinetic solubility assays are used to determine the compound’s potency at various concentrations. Two rounds of kinetic solubility assays determine gross and broad solubility (mmol/L) and finite solubility (less than 20 µmol/L) before the compound is advanced into thermodynamic solubility assays. Figure modified from Petereit A, Saal C. What is the Solubility of My Compound? Assessing Solubility for Pharmaceutical Research and Development Compounds. Am Pharm Rev. 2011; 14

The drug discovery business is changing rapidly. More pharmaceutical companies are working with smaller biotech firms to create early-stage compounds, and thus need quicker and standardized solutions to early-stage development problems.

READ ALL AT

 

http://www.dddmag.com/articles/2013/06/automating-lead-optimization?et_cid=3304624&et_rid=523035093&type=cta

 

 

by

WORLD DRUGTRACKER

Gilead Announces U.S. FDA Priority Review Designation for Sofosbuvir for the Treatment of Hepatitis C


File:PSI-7977.svg

Sofosbuvir

Isopropyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-phenoxy-phosphoryl]amino]propanoate

http://www.ama-assn.org/resources/doc/usan/sofosbuvir.pdf  –for cas no

hepatitis c

 

Jun. 7, 2013– Gilead Sciences, Inc. today announced that the U.S. Food and Drug Administration (FDA) has granted priority review to the company’s New Drug Application (NDA) for sofosbuvir, a once-daily oral nucleotide analogue inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. The FDA grants priority review status to drug candidates that may offer major advances in treatment over existing options. Gilead filed the NDA for sofosbuvir on April 8, 2013, and FDA has set a target review date under the Prescription Drug User Fee Act (PDUFA) of December 8, 2013.

The data submitted in this NDA support the use of sofosbuvir and ribavirin (RBV) as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with RBV and pegylated interferon (peg-IFN) for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection.

Sofosbuvir is an investigational product and its safety and efficacy have not yet been established.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

Sofosbuvir (formerly PSI-7977 or GS-7977) is an experimental drug candidate for the treatment of hepatitis C.[1] It was discovered at Pharmasset and then acquired for development by Gilead Sciences. It is currently in Phase III clinical trials.[2]

Sofosbuvir is a prodrug that is metabolized to the active antiviral agent 2′-deoxy-2′-α-fluoro-β-C-methyluridine-5′-monophosphate.[3]

Sofosbuvir is a nucleotide analogue inhibitor of the hepatitis C virus (HCV) polymerase.[4] The HCV polymerase or NS5B protein is a RNA-dependent RNA polymerase critical for the viral cycle.

Sofosbuvir is being studied in combination with pegylated interferon and ribavirin, with ribavirin alone, and with other direct-acting antiviral agents.[5] It has shown excellent clinical efficacy when used either with pegylated interferon/ribavirin or in interferon-free combinations. In particular, combinations of sofosbuvir with NS5A inhibitors, such as daclatasvir or GS-5885, have shown sustained virological response rates of up to 100% in people infected with HCV.[6]

Data from the ELECTRON trial showed that a dual interferon-free regimen of sofosbuvir plus ribavirin produced a 24-week post-treatment sustained virological response (SVR24) rate of 100% for previously untreated patients with HCV genotypes 2 or 3.[7][8]

Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of sofosbuvir, ledipasvir (formerly GS-5885), and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1.[9]Gilead has developed a sofosbuvir + ledipasvir coformulation that is being tested with and without ribavirin.

  1. Sofia, M. J.; Bao, D.; Chang, W.; Du, J.; Nagarathnam, D.; Rachakonda, S.; Reddy, P. G.; Ross, B. S. et al. (2010). “Discovery of a β-d-2′-Deoxy-2′-α-fluoro-2′-β-C-methyluridine Nucleotide Prodrug (PSI-7977) for the Treatment of Hepatitis C Virus”. Journal of Medicinal Chemistry 53 (19): 7202–7218. doi:10.1021/jm100863xPMID 20845908edit
  2.  “PSI-7977″. Gilead Sciences.
  3.  Murakami, E.; Tolstykh, T.; Bao, H.; Niu, C.; Steuer, H. M. M.; Bao, D.; Chang, W.; Espiritu, C. et al. (2010). “Mechanism of Activation of PSI-7851 and Its Diastereoisomer PSI-7977″Journal of Biological Chemistry 285 (45): 34337–34347.doi:10.1074/jbc.M110.161802PMC 2966047PMID 20801890edit
  4.  Alejandro Soza (November 11, 2012). “Sofosbuvir”. Hepaton.
  5.  Tom Murphy (November 21, 2011). “Gilead Sciences to buy Pharmasset for $11 billion”Bloomberg Businessweek.
  6.  http://www.gilead.com/pr_1757156
  7.  AASLD: PSI-7977 plus Ribavirin Can Cure Hepatitis C in 12 Weeks without Interferon. Highleyman, L. HIVandHepatitis.com. 8 November 2011.
  8.  Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C. Gane, E et al. New England Journal of Medicine 368:3444. January 3, 2013.
  9.  CROI 2013: Sofosbuvir + Ledipasvir + Ribavirin Combo for HCV Produces 100% Sustained Response. Highleyman, L. HIVandHepatitis.com. 4 March 2013.

Eating Broccoli Reduces Risk of Cardiovascular Disease, Promotes Heart Health


4212009307_621d82e912_o_5

by Elizabeth Renter , MY SCIENCE ACADEMY

It’s not good enough to know that vegetables like broccoli are healthful; we need to know specifically what sort of benefits they deliver, how they deliver those benefits and how we can make the most of them.

read all at

http://myscienceacademy.org/2013/06/07/eating-broccoli-reduces-risk-of-cardiovascular-disease-promotes-heart-health/

Otsuka Pharmaceutical Submits New Drug Application in Japan for Tolvaptan for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)


TOLVAPTAN

may 30 2013

  • Tolvaptan was discovered by Otsuka in Japan, and its primary results from a global clinical trial involving 1,400 ADPKD patients from 15 countries, which demonstrated a statistically significant reduction in the rate of total kidney volume, were published in New England Journal of Medicine in 2012. It is also currently under a fast track review in the US, following our announcement of FDA accepting to review the application in April 2013.
  • ADPKD is a hereditary and often physically and mentally burdensome disease characterized by the development of multiple cysts in the kidneys. ADPKD is often associated with pain, hypertension, decreased kidney function and ultimately, kidney failure that may result in hemodialysis or kidney transplantation.
  • There are estimated to be approximately 31,000 ADPKD patients in Japan, and the diagnosed prevalence is estimated to be between 1:1000 and 1:4000 globally.

(Tokyo, Japan, May 30, 2013) – Otsuka Pharmaceutical Co., Ltd. Today announced it filed an application with the Pharmaceutical and Medical Devices Agency in Japan (PMDA) to market its novel compound tolvaptan for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Phase III clinical trial results that form the basis of the regulatory filing were published in the New England Journal of Medicine in November 2012. The MHLW has designated tolvaptan as an Orphan Drug.http://www.otsuka.co.jp/en/release/2013/0603_02.html

Tolvaptan (INN), also known as OPC-41061, is a selective, competitive vasopressin receptor 2 antagonist used to treat hyponatremia (low blood sodium levels) associated withcongestive heart failurecirrhosis, and the syndrome of inappropriate antidiuretic hormone(SIADH). Tolvaptan was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2009, and is sold by Otsuka Pharmaceutical Co. under the trade name Samsca and in India is manufactured & sold by MSN laboratories Ltd. under the trade name Tolvat & Tolsama.

Tolvaptan is also in fast-track clinical trials[2] for polycystic kidney disease. In a 2004 trial, tolvaptan, when administered with traditional diuretics, was noted to increase excretion of excess fluids and improve blood sodium levels in patients with heart failure without producing side effects such as hypotension (low blood pressure) or hypokalemia(decreased blood levels of potassium) and without having an adverse effect on kidney function.[3] In a recently published trial (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948) the study met its primary and secondary end points. Tolvaptan, when given at an average dose of 95 mg per day over a 3-year period, slowed the usual increase in kidney volume by 50% compared to placebo (2.80% per year versus 5.51% per year, respectively, p<0.001) and reduced the decline in kidney function when compared with that of placebo-treated patients by approximately 30% (reciprocal serum creatinine, -2.61 versus -3.81 (mg/mL)-1 per year, p <0.001)[4]

Chemical synthesis:[5] Tolvaptan.png

  1. Shoaf S, Elizari M, Wang Z, et al. (2005). “Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias”. J Cardiovasc Pharmacol Ther 10 (3): 165–71. doi:10.1177/107424840501000304PMID 16211205.
  2.  Otsuka Maryland Research Institute, Inc.
  3. Gheorghiade M, Gattis W, O’Connor C, et al. (2004). “Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial”. JAMA 291 (16): 1963–71. doi:10.1001/jama.291.16.1963PMID 15113814.
  4. (2012) Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease
  5. Kondo, K.; Ogawa, H.; Yamashita, H.; Miyamoto, H.; Tanaka, M.; Nakaya, K.; Kitano, K.; Yamamura, Y.; Nakamura, S.; Onogawa, T.; et al.; Bioor. Med. Chem. 1999, 7, 1743.
  6. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm?source=govdelivery
  • Gheorghiade M, Niazi I, Ouyang J et al. (2003). “Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial”. Circulation 107 (21): 2690–6. doi:10.1161/01.CIR.0000070422.41439.04.PMID 12742979.

New study reveals Iron supplementation may help Velcade work better


bortezomib

read at

http://trialx.com/curetalk/2013/06/new-study-reveals-iron-supplementation-may-help-velcade-work-better/

Bortezomib (INN, originally codenamed PS-341; marketed as Velcade by Millennium Pharmaceuticals) is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease.

File:Bortezomib-from-PDB-2F16-3D-balls.png

Bortezomib was originally synthesized in 1995 (MG-341) at a company called Myogenics, which soon changed its name to ProScript. After promising preclinical results, the drug (PS-341) was tested in a small Phase I clinical trial on patients with multiple myeloma cancer. ProScript ran out of money and was bought by Leukosite in May 1999. Leukosite in turn was bought by Millennium Pharmaceuticals in October 1999. At this point in time, the project had low priority amongst other projects at the company. This changed significantly when one of the first volunteers to receive the drug in the clinical trial achieved a complete response and were still alive four years later. At the time this was a remarkable result. Later clinical experimentation indicates the possibility of a complete response in 15% of patients in a similar condition, when treated with bortezomib.

In May 2003, seven years after the initial synthesis, bortezomib (Velcade) was approved in the United States by the Food and Drug Administration (FDA) for use in multiple myeloma, based on the results from the SUMMIT Phase II trial.

 

Another commercially available bortezomib product – Bortenat (Natco Pharma, India), reportedly contains substantially more active entity than declared, potentially and even more resulting in increase toxicity. Moreover, Bortenat has some other chemical and formulation deviations from the registered ethic product Velcade (Millennium Pharmaceuticals and Janssen-Cilag), with unclear clinical impact.

 

Pharmacology

 

Bortezomib bound to the core particle in a yeast proteasome. The bortezomib molecule is in the center colored by atom type (boron = pink, carbon = cyan, nitrogen = blue, oxygen = red), surrounded by the local protein surface. The blue patch is catalytic threonine residue whose activity is blocked by the presence of bortezomib.

 

Structure

 

The drug is an N-protected dipeptide and can be written as Pyz-Phe-boroLeu, which stands for pyrazinoic acid, phenylalanine and Leucine with a boronic acid instead of a carboxylic acid. Peptides are written N-terminus to C-terminus, and this convention is used here even though the “C-terminus” is a boronic acid instead of a carboxylic acid.