甲磺酸酚妥拉明口服液在健康志愿者体内的药代动力学及生物等效性研究-药理学专业论文.docxVIP

温州医学院硕士学位论文 温州医学院硕士学位论文 95．5～105．9％：均符合生物等效性的要求。 结论①本研究采用的反相一高效液相色谱法快速、简便、灵敏、准确，可用于 血浆甲磺酸酚妥拉明的检测和临床药代动力学研究。②试验制剂与参比制剂的 人体相对生物利用度符合要求。③试验制剂与参比制剂的人体相对生物利用度 为94．1±9．6％，试验制剂与参比制剂具有生物等效性。 陕键词l 甲磺酸酚妥拉明；药代动力学；相对生物利用度：生物等效性；高效 液相色谱法 温州医学院硕士学位论文Study 温州医学院硕士学位论文 Study of the Pharmacokinetics and BioequivaIence of Phentolamine Mesilate Oral Solution in Healthy Volunteers ABSTRACT Objeetive The HPLC was used to study on the the pharmacokinetics，relative bioavailability and bioequivalence of phent01amine mesilate oral solution in Chinese healthy volunteers． Methods①Phentolamine mesilate of blood plasma was extracted with acetic ether and N-hexane detected with HPLC Agi lent l100．Chromate bar ZORBAX SB—C18(4．6×250啪，5u m，Agilent，USA)，guard column SB—C18 (4．6×12．5 mm，5u m，Agilent，USA)，mobile phase acetonitrile一0．15 mol·L—NaH2PO．一H20一10 mmol·L。SDS(33：25：40：2，v／v／v／v)，flow rate Iml／min，column temperature 50℃，detection wave length 278 nm， reference wave length 380 nm，detection sensitivity 0．01 mAU， carbamazepine as internal standard． ②20 heal thy volunteers were given orally at random double—cross phentolamine mesi late solution(test agent，T)and phentolamine mesi late dispersible tablets(reference agent， R)60mg every 2 weeks．Venous blood was taken in multipoint 12 hour after administration．The concentration of Phentolamine mesilate in blood plasma was detected wi th HPLC． Relati ve bioavai labi 1 i ty and bioequivalence of the 2 preparations were calculated wi th DAS pharmacokinetics program，AUC(0-12)，AUC‘o—i。r， and C。。were got with ANOVA， double and single side T test．rank sum test with T。Results@The linear correlation of phentelamine concentrations was good at 2．5～i00u g·L1 (r=O，9999；the lowest value detectable 1．8 p g·L～；average relative recovery i00．5±3．52％，average absolute recovery 75．397±3．24％： precision variability coefficient of intra—day and inter—day 5．40± 3．32％and 7．35±3．13％．respectively．The absolute recovery of carbamazepine is 78．87±4．29％；variation o