CAJ | 학술논문

研究醋酸艾塞那肽(exendin-4)在Wistar大鼠体内的药物代谢动力学,组织分布以及排泄特征.IODOGEN(四氯二苯基苷脲)法制备125I-exendin-4,大鼠皮下或静脉注射125I-exendin-4,以放射性核素示踪动力法检测血液中的药物浓度,由非房室模型评价药物动力学参数.同时研究了大鼠皮下注射125I-exendin-4后的组织分布和排泄.大鼠皮下注射nsI_exendin-4后Tmax和t1/2分别是(0.25±0.02)h和(1.284±0.14)h,绝对生物利用度为(65.5±10.2)%;125I-exendin-4的分布快速而广泛,其中以肾脏中最高,而在脑组织中只有微量125I-exendin-4;125I-exendin-4主要随尿液排泄.实验结果与国外公布的实验数据基本一致.醋酸艾塞那肽在大鼠中的药物代谢动力学参数为临床试验提供了科学依据.
연구작산애새나태(exendin-4)재Wistar대서체내적약물대사동역학,조직분포이급배설특정.IODOGEN(사록이분기감뇨)법제비125I-exendin-4,대서피하혹정맥주사125I-exendin-4,이방사성핵소시종동역법검측혈액중적약물농도,유비방실모형평개약물동역학삼수.동시연구료대서피하주사125I-exendin-4후적조직분포화배설.대서피하주사nsI_exendin-4후Tmax화t1/2분별시(0.25±0.02)h화(1.284±0.14)h,절대생물이용도위(65.5±10.2)%;125I-exendin-4적분포쾌속이엄범,기중이신장중최고,이재뇌조직중지유미량125I-exendin-4;125I-exendin-4주요수뇨액배설.실험결과여국외공포적실험수거기본일치.작산애새나태재대서중적약물대사동역학삼수위림상시험제공료과학의거.
To characterize the preelinical pharmacokinetics，tissue distribution and excretion profiles of exendin-4 in healthy Wistar rats were studied.Exendin-4 was radioiodinated by the IODOGEN (1，3，4，6-tetrachloro-3 alpha，6 alphadiphenylglucohiril)method.Pharmaeokinetie properties of 125I-exendin-4 were examined after a single s.c.and I.v.injection，respectively.Tissue distribution and urinary，fecal，and biliary excretion patterns of 125I-exendin-4 were also investigated following a single s.c.injection.Exendin-4 was rapidly distributed and cleared with t1/2 of (0.48 ± 0.03) h after a single I.v.injection.Following a single s.c.administration，exendin-4 exhibited rapid and considerable absorption with Tmax of (0.25 4- 0.02) h and declined with the elimination t1/2 of (1.28 ± 0.14) h.The absolute bioavailability was (65.5 ± 10.2) %.The radioactivity was widely distributed and rapidly diminished in most tissues.The kidney contained the highest radioactivity and the distribution of 125I-exendin-4 to the brain was minimal.The major elimination route was urinary excretion.The pharmacokinetic properties of exendin-4 obtained from the present study closely matched those reported in previous studies in rats.Pharmacokinetics profiles of exendin-4 in rats are warranted for the design of future clinical trials.