Integration analysis between RNA editing and circadian clock system for elucidation of interindividual variation of drug pharmacokinetics

KAKEN

About This Project

Japan Grant Number
JP18H04019 (JGN)
Funding Program
Grants-in-Aid for Scientific Research
Funding Organization
Japan Society for the Promotion of Science

Kakenhi Information

Project/Area Number
18H04019
Research Category
Grant-in-Aid for Scientific Research (A)
Allocation Type
  • Single-year Grants
Review Section / Research Field
  • Medium-sized Section 47:Pharmaceutical sciences and related fields
Research Institution
  • Kyushu University
Project Period (FY)
2018-04-01 〜 2022-03-31
Project Status
Completed
Budget Amount*help
34,190,000 Yen (Direct Cost: 26,300,000 Yen Indirect Cost: 7,890,000 Yen)

Research Abstract

Daily variations in biological functions are important factors affecting the efficacy and toxicity of drugs; a large number of drugs cannot be expected to have the same potency at different administration times. Dosing time-dependent differences in the therapeutic effects of drugs are, at least in part, due to diurnal changes in drug disposition such as absorption, distribution, metabolism and elimination. The expression and function of several xenobiotic transporters and drug metabolism enzymes exhibit diurnal variation, resulting in dosing time-dependent differences in drug disposition. The present study demonstrated that adenosine deaminase acting on RNA (ADAR) was involved in the circadian regulation of xenobiotic transporters and drug metabolism enzymes in human renal proximal tubular epithelial cells and hepatic cells. ADAR1 regulate the expression of these pharmacokinetics-related factors through modulating the transcription, translation, formation of splicing variant.

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