Induction of hepatic drug-metabolizing enzymes by probenecid in rats
Issued Date
1992
Copyright Date
1992
Resource Type
Language
eng
File Type
application/pdf
No. of Pages/File Size
x, 70 leaves
Access Rights
open access
Rights
ผลงานนี้เป็นลิขสิทธิ์ของมหาวิทยาลัยมหิดล ขอสงวนไว้สำหรับเพื่อการศึกษาเท่านั้น ต้องอ้างอิงแหล่งที่มา ห้ามดัดแปลงเนื้อหา และห้ามนำไปใช้เพื่อการค้า
Rights Holder(s)
Mahidol University
Bibliographic Citation
Thesis (M.Sc. (Pharmacology))--Mahidol University, 1992
Suggested Citation
Aranya Jarusuttirux Induction of hepatic drug-metabolizing enzymes by probenecid in rats. Thesis (M.Sc. (Pharmacology))--Mahidol University, 1992. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/103195
Title
Induction of hepatic drug-metabolizing enzymes by probenecid in rats
Alternative Title(s)
การเหนี่ยวนำเอ็นไซม์ที่ทำลายยาของตับโดยโปรเบเนซิด (Probenecid) ในหนู
Author(s)
Abstract
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.
Description
Pharmacology (Mahidol University 1992)
Degree Name
Master of Science
Degree Level
Master's degree
Degree Department
Faculty of Science
Degree Discipline
Pharmacology
Degree Grantor(s)
Mahidol University