薬理と治療

Abstract

Background Epoetin beta pegol(MIRCERA)is a chemically synthesized erythropoiesis stimulating agent with the integration of epoetin beta and linear methoxy polyethylene glycol (mPEG). Serum MIRCERA concentration is determined by sandwich enzyme-linked immunosorbent assay using both anti human epoetin antibody and anti mPEG antibody(MIRCERA determination method). However, this method is not available commercially in Japan. We sought to establish whether RIA2 antibody assay, which is usually used for determining serum epoetin concentration by anti epoetin rabbit antibody, could determine serum MIRCERA concentration appropriately. Methods ①10 kinds of standard solution with various MIRCERA concentrations from 10000 to 0 ng/mL were prepared. Each solution was determined by RIA2 antibody assay as epoetin concentration and the correlation between MIRCERA concentration and epoetin concentration was tested. Then, its conversion formula was estimated. ②100 or 150 μg MIRCERA were administrated intravenously to 8 hemodialysis patients. Serum epoetin concentration was determined by RIA2 antibody assay, then, it was converted to MIRCERA concentration. Area under the serum MIRCERA concentration-time curve(AUClast)and half-lives(t1/2)were estimated. ③These AUClast and t1/2 were compared to those obtained previously by MIRCERA determination method. Results AUClast by RIA2 antibody assay after administration of 100 and 150 μg were respectively equivalent to 42.6 and 40.6% of those obtained by MIRCERA determination method. However, t1/2 were 169 and 129 hours by RIA2 method, these values were similar to those obtained by MIRCERA determination method Conclusions As the concentration determined by RIA2 antibody assay reflected the long t1/2 which is the pharmacokinetic feature of MIRCERA successfully, our novel method is substitutable clinically.