흰쥐에 있어서 PEG-헤모글로빈 SB1의 단회정맥투여 약물동태

Pharmacokinetics of a New PEG-hemoglobin SB1 for Single Intravenous Administration to Rats

An intravenous pharmacokinetics for a new red cell substitute, PEG-hemoglobin SB1, was studied in SD rats. Total-hemoglobin and its metabolite methemoglobin in the plasma were determined using a spectrophotometer. The limit of quantitation was 0.01g/dL and the C.V for interday assay reproducibility was less than 6%. Upon intravenous administration of anticipated clinical dose, 10ml (0.7gHb)/kg, plasma concentration curve of total-hemoglobin was well described by one-compartment model. The t1/2, CLt, Vd and AUC0-48h were 8.23+/-0.96hr, 0.06+/-0.01dL/hr/kg, 0.66+/-0.05dL/kg and 13.6+/-1.01g.hr/dL, respectively, in male rats(n=5, mean+/-SD). Those parameters in female rats were 9.21+/-2.31hr, 0.06+/-0.01dL/hr/kg, 0.79+/-0.08dL/kg and 13.0+/-2.36g.hr/dL, respectively. Similar kinetic profiles between males and females were also obtained from other parameters. Small amount of methemoglobin, an oxidative metabolite of SB1, was detected in the plasma of both sexes, where the AUC0-48hr,m and t1/2,m were approximately 1.5g.hr/dL and 20hr, respectively. The present work provides a critical kinetic data for the effective clinical applications of PEG-hemoglobm SB1.