摘要:

Background and objectiveDifferent types of hydroxyethyl starch (HES) affect blood coagulation differently. We studied the effects of HES 130/0.4 on coagulation in major orthopaedic surgery in relation to the pharmacological parameterin vivomolecular weight.Methods52 patients were randomly allocated to either HES 130/0.4 (6%, mean molecular weight 130 kDa, molar substitution 0.4) or HES 200/0.5 (6%, control) in a double-blind fashion. Colloidal volume requirements for intra- and postoperative haemodynamic stabilisation were compared. Safety analyses of this pharmacological study included a comparison of coagulation factor tests,in vivomolecular weight, and HES plasma concentrations.ResultsThe colloidal volumes given were similar at the end of surgery (1602 ± 569 for HES 130/0.4 vs 1635 ± 567mL for HES 200/0.5), 5h later (1958 ± 467 vs 1962 ± 398mL), and up to the first postoperative day (2035 ± 446 vs 2000 ± 424mL). HESin vivomolecular weight at the end of surgery was 88 707 ± 13 938 versus 158 374 ± 33 933Da (p < 0.001) and 5h later was 86 663 ± 16 126 versus 136 299 ± 26 208Da (p < 0.001). In parallel to the lowerin vivomolecular weight, factor VIII and von Willebrand factor returned to almost normal in the HES 130/0.4 group up to 5h postoperatively, but not in the control group (p < 0.05). Residual HES plasma concentrations after 24h were low in the HES 130/0.4 group (1.0 mg/mL), but higher in the control group (2.6 mg/mL).ConclusionHES 130/0.4 and HES 200/0.5 were found to be similar with regard to volume efficacy. Sensitive coagulation parameters returned more rapidly to normal in the HES 130/0.4 group. Lowerin vivomolecular weight and more rapid excretion of HES 130/0.4 are the likely explanations for the smaller influence on coagulation in this group.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the β2-adrenoceptor agonist formoterol [eformoterol]. This isomer contains two chiral centres and is being developed as an inhaled preparation for the treatment of respiratory disorders. Sepracor believes that arformoterol has the potential to be a once-daily therapy with a rapid onset of action and a duration of effect exceeding 12 hours.In 1995, Sepracor acquired New England Pharmaceuticals, a manufacturer of metered-dose and dry powder inhalers, for the purpose of preparing formulations of levosalbutamol and arformoterol.Phase II dose-ranging clinical studies of arformoterol as a longer-acting, complementary bronchodilator were completed successfully in the fourth quarter of 2000. Phase III trials of arformoterol began in September 2001. The indications for the drug appeared to be asthma and chronic obstructive pulmonary disease (COPD). However, an update of the pharmaceutical product information on the Sepracor website in September 2003 listed COPD maintenance therapy as the only indication for arformoterol.In October 2002, Sepracor stated that two pivotal phase III studies were ongoing in 1600 patients. Sepracor estimates that its NDA submission for arformoterol, which is projected for the first half of 2004, will include approximately 3000 adult subjects.Sepracor stated in July 2003 that it had completed more than 100 preclinical studies and initiated or completed 15 clinical studies for arformoterol inhalation solution for the treatment of bronchospasm in patients with COPD. In addition, Sepracor stated that the two pivotal phase III studies in 1600 patients were still progressing.In 1995, European patents were granted to Sepracor for the use of arformoterol in the treatment of asthma, and the US patent application was pending.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

CHF 3381 is an NMDA antagonist and monoamine oxidase inhibitor under development with Chiesi for the treatment of neuropathic pain. Preclinical studies show that the agent acts as a reversible and competitive inhibitor of human monoamine oxidases A and B.At the 1st Annual BioPartnering North America (BPN-2003) it was stated that CHF 3381 is being evaluated for the treatment of neuropathic pain. Preliminary data also suggested that CHF 3381 may have neuroprotective activity.In June 2003, Chiesi announced the completion of a phase I trial in France, and is proceeding with a proof-of-concept study in Denmark.[1]CHF 3381 is covered by European patent application EP 951465 (expires on 15 July 2017), and US patent No. 6,114,391 (issued on 5 September 2000). Other patents are granted or pending in 20 countries. Chiesi also has rights to the European patent application for use of glycinamide derivatives (including CHF 3381) in the treatment of chronic pain.[2]

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Ecraprost [AS 013, Circulase™] is a prodrug of prostaglandin E1within lipid microspheres that is being developed in Japan by Mitsubishi Pharma Corporation and Asahi Glass. It was originally in development with Welfide Corporation. On 1 October 2001, Welfide Corporation (formerly Yoshitomi) merged with Mitsubishi-Tokyo Pharmaceuticals to form Mitsubishi Pharma Corporation. The new company is a subsidiary of Mitsubishi Chemical.Taisho and Seikagaku Corporation had been involved in the development of ecraprost but discontinued their licences to do so. The effects of ecraprost on reperfusion injury, in preclinical studies, had been reported by Taisho.Ecraprost is in phase II in Japan and was in phase II in Europe for the treatment of peripheral arterial disease. It was also in a phase II study in the treatment of diabetic neuropathies. However, this is no longer an active indication.A phase III trial using a lipid emulsion of ecraprost [Circulase™] is underway with Mitsubishi Pharma Corporation in the US, using ecraprost for the treatment of patients with severe peripheral arterial disease, which, because of decreased blood flow to the extremities, can lead to painful ulcers on the legs and feet and subsequent amputation. Alpha Therapeutic Corporation (a former subsidiary of Mitsubishi Pharma) was initially involved in trials of ecraprost in the US, but this responsibility has been taken over by the parent company.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Exenatide [AC002993, AC2993A, AC 2993, LY2148568, exendin 4], a glucagon-like peptide-1 (GLP-1) agonist, is a synthetic exendin 4 compound under development with Amylin Pharmaceuticals for the treatment of type 2 diabetes.Both exendin 4 and its analogue, exendin 3, are 39-amino acid peptides isolated fromHeloderma horridumlizard venom that have different amino acids at positions 2 and 3, respectively. Exendins are able to stimulate insulin secretion in response to rising blood glucose levels, and modulate gastric emptying to slow the entry of ingested sugars into the bloodstream.Amylin Pharmaceuticals acquired exclusive patent rights for the two exendin compounds (exendin 3 and exendin 4) from the originator, Dr John Eng (Bronx, NY, US).On 20 September 2002, Amylin and Eli Lilly signed a collaborative agreement for the development and commercialisation of exenatide for type 2 diabetes. Under the terms of the agreement, Eli Lilly has paid Amylin a licensing fee of $80 million and bought Amylin's stock worth $30 million at $18.69 a share. After the initial payment, Eli Lilly will pay Amylin up to $85 million upon reaching certain milestones and also make an additional payment of up to $130 million upon global commercialisation of exenatide. Both companies will share the US development and commercialisation costs, while Eli Lilly will pick up up to 80% of development costs and all commercialisation costs outside the US.Amylin and Eli Lilly will equally share profit from sales in the US, while Eli Lilly will get 80% of the profit outside the US and Amylin will get the rest. This agreement has also enabled Amylin to train its sales force to co-promote Lilly's human growth hormone Humatrope®.[1]Alkermes will receive research and development funding and milestone payments, and also a combination of royalty payments and manufacturing fees based on product sales. Alkermes undertakes the responsibility for the development of several initial formulations of the long-acting drug and manufacturing of the final product, while Amylin will be responsible for clinical trials, regulatory filings and worldwide marketing. The goal of the exenatide LAR programme is to develop a once-a-month injectable formulation of exenatide.In November 2003, Amylin announced positive results from the second of three pivotal, phase III studies that evaluated the effects of exenatide in combination with sulfonylureas in 377 randomised patients with type 2 diabetes. The design of the study was similar to that from the first study.[2]The final third phase III study of exenatide was completed in November 2003. This study investigated the effects of exenatide in combination with metformin and sulfonylureas. Amylin and Eli Lilly announced that all of the pivotal phase III trials met the primary glucose control endpoint as measured by glycosylated haemoglobin.[3]An NDA submission for exenatide is projected for mid-2004.A phase II, dose-ascending study in patients with type 2 diabetes was initiated in June 2002.[4]This multicentre (US), double-blind, placebo-controlled study evaluated the safety, tolerability and the pharmacokinetic profile of exenatide LAR in up to 100 patients with type 2 diabetes.A phase I study of exenatide LAR began in Europe in March 2001 and was completed in Q3 2001. A long-acting, sustained-release formulation of exenatide lowered both pre- and post-meal glucose concentration during a 24h period in patients with type 2 diabetes.In November 2002, analysts at Prudential Financial estimated that exenatide, pending approval, has the potential to reach sales of $US477 million in 2006.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Fozivudine [BM 211290, fozivudine tidoxil, FZT, HDP 990002, W 09726867] is a thioether lipid conjugate of zidovudine (AZT) in clinical development with Heidelberg Pharma Holdings for the potential treatment of HIV infection. Heidelberg Pharma's proprietary Linker-Cleavag-Enzyme Technology (LCE_Technology) is used to conjugate specific carriers to parent compounds, significantly improving their pharmacological, toxicological and/or clinical profile.LCE_Technology was originated at Boehringer Mannheim, which was acquired by, and integrated into, Roche. In 1999, when Heidelberg Pharma was founded, following a management buy-out from Roche Diagnostics GmbH, the new company acquired full ownership of the intellectual property and documentation related to various proprietary compounds, the LCE_Technology and its applications.According to Heidelberg Pharma's pipeline, published in August 2003, the product candidate, HDP 99.0002 (the company-specific code for fozivudine) will be in phase III development until early 2006, at which time the company hopes to file an NDA.A phase II study of fozivudine in 72 antiretroviral-naive patients with HIV infection was completed in the US and France by Roche.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Huperzine A, an alkaloid isolated fromHuperzia serrata, is a putative nootropic agent developed by the Chinese Academy of Sciences. Huperzine A is currently in phase III trials in China for the treatment of patients with Alzheimer's disease. The mechanism of action of huperzine A is suggested to be facilitated through the slow reversible inhibition of acetylcholinesterase.Marco Hi-Tech Joint Venture has exclusive worldwide marketing and distribution rights to huperzine A. Marco Hi-Tech Joint Venture is a corporation principally owned by Hi-Tech Pharmacal and Marco International, a global trading and finance firm formed to import huperzine A from China. Marco Hi-Tech Joint Venture also has rights to synthetic analogues of huperzine A.In July 2003, Savient Pharmaceuticals acquired the exclusive rights from Marco Hi-Tech to market huperzine A in Europe and the US.[1]Clinical trials of huperzine A in elderly patients with age-associated memory loss are underway in the US, and a phase II study funded by an NCI grant is being planned.[1]

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx®drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1–3μ in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx®insulin Diabetes Management System (iDMS), AERx®iDMS, instructs the user on breathing technique to achieve the best results.Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx®iDMS, NN 1998].Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx®device.Both companies will explore the possibilities of the AERx®platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area.In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx®drug delivery system.Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin.Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal insulin administered once or twice daily.[1]In 2003, the US FDA adopted new GMP guidelines requiring sterile production of inhalation products and their devices. Novo Nordisk, therefore, will need to repeat phase III studies following device optimisation. These studies may begin at the end of 2004 and will include efficacy studies for 6–12 months and safety studies for up to 2 years (Lehman Brothers, Equity research, 7 August 2003).A phase IIb, 12-week clinical trial in 107 patients with type 2 diabetes was completed in the US. This trial was designed to compare the safety and efficacy of pulmonary insulin delivered via AERx®iDMS, with intensified treatment with subcutaneous insulin administered at mealtimes. The results of the study positively compared pulmonary insulin with intensified subcutaneous insulin.Aradigm Corporation has a total of 85 patents pertaining to its proprietary AERx®drug delivery system. Among those granted patents, 18 patents cover pulmonary insulin formulation including the method of patient breathing technique during pulmonary delivery of insulin. This patent guides patients on how to breathe in certain defined ways to achieve an effective amount and reproducibility of blood levels of insulin.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS