Comparative inhibitory effects of mefloquine and primaquine on hepatic drug-metabolizing enzymes
Issued Date
1988
Copyright Date
1988
Resource Type
Language
eng
File Type
application/pdf
No. of Pages/File Size
xi, 120 leaves : ill.
Access Rights
open access
Rights
ผลงานนี้เป็นลิขสิทธิ์ของมหาวิทยาลัยมหิดล ขอสงวนไว้สำหรับเพื่อการศึกษาเท่านั้น ต้องอ้างอิงแหล่งที่มา ห้ามดัดแปลงเนื้อหา และห้ามนำไปใช้เพื่อการค้า
Rights Holder(s)
Mahidol University
Bibliographic Citation
Thesis (M.Sc. (Pharmacology))--Mahidol University, 1988
Suggested Citation
Thananda Sukhumanan Comparative inhibitory effects of mefloquine and primaquine on hepatic drug-metabolizing enzymes. Thesis (M.Sc. (Pharmacology))--Mahidol University, 1988. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/103352
Title
Comparative inhibitory effects of mefloquine and primaquine on hepatic drug-metabolizing enzymes
Alternative Title(s)
การเปรียบเทียบผลของยาเมฟบอควิน (Mefloquine) และไพรมาควิน (Primaquine) ต่อเอ็นซัยม์ที่ทำหน้าที่เปลี่ยนแปลงยาในตับ
Author(s)
Abstract
The effect of mefloquine (MQ) on hepatic drugmetabolizing enzymes in the rat had been comapred with that of primaquine (PQ) both in vitro and in vivo. For in vitro studies using type I compounds (aminopyrine and hexobarbital), it was found that MQ inhibited only aminopyrine N-demethylase whereas PQ inhibited both aminopyrine N-demethylase and hexobarbital oxidase. At the concentration of 10(4) M these two antimalarials produced comparable per cent inhibition (approximately 54%) on aminopyrine N-demethylase, while at the lower concentration PQ produced greater inhibition than MQ. As for type II compouds (aniline and p-chloro-N-methylaniline), MQ exerted a very weak inhibitory effect on aniline hydroxylase (23% at 10(-4)M but had no effect on p-chloro-N-methylaniline N-demethylase. On the contrary, PQ was found to be quite a potent inhibitor of anilline hydroxylase but to be a very weak inhibitor of p-chloro-N-methylanline N-demethylase (11% at 10(-4)M). For a reverse type I compound, p-nitroanisole, both MQ and PQ could inhigit the enzyme p-nitroanisloe-O-demethylase, though MQ was a very weak inhibitor. Kinetic studies shiwed that aminopyrine N-demethylase was inhibited noncompetitively by MQ whereas th einhibition by PQ was competitive. PQ was also found to be a noncompetitive inhibitor of hexobarbital oxidase, whilc producing a noncompetitive and competitive inhibition on aniline hydroxylase and p-chloro-N-methylaniline N-demethylase, respectively. the kinetic nature of inhibition by both MQ and PQ on the metabolism of the reverse type I compound was noncom-petitive. The results from studies in vivo were consistent with the in vitro findings. PQ (50 mg/kg, IP) was found to prolong zoxazolamine paralysis time while MQ (50mg/kg, PO) had no effect. These findings thus demonstrate that MQ is a much weaker inhibitor of hepatic drug-matabolizing enzymes than PQ.
Description
Pharmacology (Mahidol University 1988)
Degree Name
Master of Science
Degree Level
Master's degree
Degree Department
Faculty of Science
Degree Discipline
Pharmacology
Degree Grantor(s)
Mahidol University