Pharmacokinetic studies of Methylprednisolone in Rabbits by Polymeric Micelle Formulation

• Main Authors: Daniel Lei, 李克繼
• Other Authors: Jiahorng Liaw
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/61713093149840376710

碩士 === 臺北醫學大學 === 藥學系 === 93 === The purpose of thesis study was used two polymeric micelles (PM1, PM2) formulation for methylprednisolone (MP) to developed (1) prolong circulation of MP in blood and (2) enhancement of accumulation of MP in spinal cord. In physicochemical properties of two formulations (MP/PM1, MP/PM2): solubility, CMC, particle size and release rate was tested. In addition, in vitro permeations of MP/PM1 and MP/PM2 were evaluated on duodenal of rabbit. Male New Zealand rabbits received oral and a IV bolus dose of MP (MP/PM1, MP/PM2, MP/H2O). The critical micelle concentration of two formulation of PM1 and PM2 values were 0.1% and 0.01%, respectively. The solubility of MP was also observed increasing from 60µg/ml (MP/H20) to 220µg/ml (MP/PM1) and 100µg/ml (MP/PM2). Particle size was found 60nm and 10nm for PM1, PM2, respectively. MP/PM1 show slow release rate by cellulose membrane tested. After incubation of P-gp inhibitor and concentration-dependence, we found that PM1, and PM2 could modify the MP transport of duodenum from Apical to Basical direction. After IV administration of three formulation (MP/H20, MP/PM1, MP/PM2): terminal half-life (t1/2β)was increased from 76 to 514 and 428 min; clearance, from 26 to 9 and 13 mL/min; AUC0→∞, from 42 to 140 and 83.3 min‧µg/mL, respectively. After oral delivery of three formulation the terminal half-life (t1/2β) was increased from 79 (MP/H20) to 416 (MP/PM1) and 428 min(MP/PM2); clearance was decreased from 24 to 8 and 13 mL/min; AUC0→∞ was increased from 19 to 75 and 82 min‧µg/mL, respectively. After oral administration of MP/PM1 and MP/PM2 the absolute bioavailability was found 0.8 and 1.2, respectively. Finally, we could observed that PM1, PM2 could prolong the blood circulation time and enhancement of MP in spinal cord.