Amnuay ThithapandhaKrongtong YoovathawornKittima SriwatanakulAranya Jarusuttirux2025-02-032025-02-03199220251992Thesis (M.Sc. (Pharmacology))--Mahidol University, 1992https://repository.li.mahidol.ac.th/handle/20.500.14594/103195Pharmacology (Mahidol University 1992)The inductive effect of probenecid on hepatic drug-metabolizing enzymes in the rats has been studied both in vivo and in vitro. The model drugs used in this study are aminopyrine, aniline and p-nitroanisole. It was found that probenecid induced the activities of both aminopyrine N-demethylase and p-nitroanisole O-demethylase. Probenecid at 600 mg/kg, PO, twice daily for 5 days was found to produce maximum increase in the activities of both enzymes. The increased aminopyrine N-demethylase activity nted by prior administration (2 hr) of actinomycin D ( O.1mg/kg, IP, at day 1 and 4 ) but not by cyclohexinide ( 2 mg/kg, IP, at day I and 4 ). The inductive effect of aminopyrine N-demethylase reached its maximum in 4 days and declined to normal in about 5 days after cessation of the drug. Kinetic studies provided support for the concept that the enzymes from both the normal and probenecid-treated livers were the same. However, this schedule of probenecid pretreatment had no effect on aniline hydroxylase activity. The nature of hepatic drug-metabolizing enzyme stimulation by probenecid appeared to resemble that of the phenobarbital-type inducers, especially because: (1) probenecid caused a noticeable proliferation of the smooth endoplasmic reticulum; (2) the time required for maximal induction and duration of its effect were almost equal to that of phenobar bital; and (3) the changes in apparent Vmax and Km values were in the same pattern. The results from studies in vivo were also consistent with the in vitro findings. Probenecid ( 600 mg/kg, PO, twice daily for 5 days ) was found to shorten zoxazolamine paralysis time. This finding is also in accord with the results in human experiments of other investigators.x, 70 leavesapplication/pdfengผลงานนี้เป็นลิขสิทธิ์ของมหาวิทยาลัยมหิดล ขอสงวนไว้สำหรับเพื่อการศึกษาเท่านั้น ต้องอ้างอิงแหล่งที่มา ห้ามดัดแปลงเนื้อหา และห้ามนำไปใช้เพื่อการค้าDrugs -- metabolismProbenecidEnzyme InductionMaster ThesisMahidol University