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http://www.hereditaryangioedema.com/phamplet.htm
البحث القادم مكان الدواء و اسمه العلمي بالون الاحمر
Cetor(R), A New C1-Inhibitor Concentrate and Its Use for Treating HAE Type I and AML.
A.H.L. Koenderman, H. Hiemstra, J. Over, H.W. Eijkhout, M.H. Tissing, C.E. Hack, A. Kleine#& W.Th. Hermens# & P.W.F. Strengers. CLB, Sanquin Blood Supply Foundation, Plesmanlaan 125, 1066 CX Amsterdam, & #Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands. [123]
At CLB a C1-inhibitor concentrate of high-purity has been developed. The manufacturing process is based on DEAE-Sepharose FF, PEG precipitation and Cm-Sepharose FF steps. Virus reduction steps consist of PEG precipitation and pasteurization for 10 hours at 60 oC. An additional 15 nm filtration step has also been developed, but will be implemented in the process in a later stage.
The product was clinically evaluated in patients with hereditary angioedema (HAE), type I. In pilot transfusions, the clinical tolerance was tested. No complications were found. To analyze the pharmacokinetic parameters, three lots of the C1-inhibitor concentrate were infused in 9 patients (total of 10 transfusions) with doses of 5 - 43 U per kg body weight. The in vivo recovery after transfusion of C1-inhibitor was 74b% (SD = 13%; n=10). Administration of one unit C1-inhibitor per kg body weight led to an in vivo response corresponding to 0.016 U per ml plasma (SD = 0.003 U per ml; n=10). The volume of distribution was 81 +/- 17 h and a clearance of 1.3 +/- 0.3 ml/h/kg (n=4) were found.
The product is licensed in Netherlands since June 1997 (brand name CetorR) for the treatment of HAE. However, there is now accumulating evidence from studies in animals and patients suggesting that the adminsitration of C1-inhibitor may have a beneficial effect in a number of other clinical conditions such as sepsis, cytokine induced vascular leak syndrome or myocardial infarction (AMI) (1). An important determinant in the development of heart failure after AMI is the amount of necrotic tissue in the jeopardized myocardium. Early reperfusion of ischemic myocardium itself may induce an inflammatory reaction, which amongst others involves activation of complement. This ischaemic-reperfusion injury may damage the cardiac tissue and limit the beneficial effects of a restored circulation. In studies at CARIM, we observed in a dog model of AMI that i.v. administration of human C1-inhibitor at a dose of 500 - 1000 U per dog (approx. 25 kg) at 2 hours and 8 hours after permanent coronary artery occlusion significantly ( up to 50%) reduces infarct size as assessed at 48 hours after the occlusion. This and other animal studies show an important cardioprotective effect of C1-inhibitor in various experimental models for AMI. Whether a similar effect may occur in humans with AMI is currently studied in a trial of limited size (n=10) of which the results will be presented.
1. Hack, C.E., C1-esterase inhibitor: an anti-inflammatory agent. Biomedical Progress, 11, 57 - 61, (1998).