tailieunhanh - báo cáo hóa học:" Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học đề tài : Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety | Ido et al. Journal of Translational Medicine 2011 9 55 http content 9 1 55 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Safety and pharmacokinetics of recombinant human hepatocyte growth factor rh-HGF in patients with fulminant hepatitis a phase I II clinical trial following preclinical studies to ensure safety 3 4 Akio Ido 1 Akihiro Moriuchi 1 Masatsugu Numata 1 Toshinori Murayama Satoshi Teramukai Hiroyuki Marusawa5 Naohisa Yamaji1 2 Hitoshi Setoyama1 2 Il-Deok Kim1 Tsutomu Chiba5 Shuji Higuchi6 Masayuki Yokode3 Masanori Fukushima4 Akira Shimizu7 and Hirohito Tsubouchi1 2 Abstract Background Hepatocyte growth factor HGF stimulates hepatocyte proliferation and also acts as an anti-apoptotic factor. Therefore HGF is a potential therapeutic agent for treatment of fatal liver diseases. We performed a translational medicine protocol with recombinant human HGF rh-HGF including a phase I II study of patients with fulminant hepatitis FH or late-onset hepatic failure LOHF in order to examine the safety pharmacokinetics and clinical efficacy of this molecule. Methods Potential adverse effects identified through preclinical safety tests with rh-HGF include a decrease in blood pressure BP and an increase in urinary excretion of albumin. Therefore we further investigated the effect of rh-HGF on circulatory status and renal toxicity in preclinical animal studies. In a clinical trial 20 patients with FH or LOHF were evaluated for participation in this clinical trial and four patients were enrolled. Subjects received rh-HGF mg m2 day intravenously for 12 to 14 days. Results We established an infusion method to avoid rapid BP reduction in miniature swine and confirmed reversibility of renal toxicity in rats. Although administration of rh-HGF moderately decreased BP in the participating subjects this BP reduction did not require cessation of rh-HGF or any vasopressor therapy BP returned to resting levels after the completion