Development of dosing schedule based on molecular clock mechanisms

基于分子钟机制的给药方案的制定

基本信息

批准号：
18390050
负责人：
OHDO Shigehiro
金额：
$ 10.16万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390050/
关键词：
Biological rhythm Biological clock Clock gene Chronopharmacology Chronotherapy

项目摘要

Mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-hr rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. However, many drugs are still given without regard to the time of day. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. To monitor the rhythmic marker was useful to choose the most appropriate time of day for administration of drugs that increase their therapeutic effects and/or reduce their side effects. On the other hand, several drugs can cause alterations to the 24-hr rhythms, which leads to illness and altered homeostatic regulation. We showed the disruptive effect of interferon on the rhythm of locomotor activity, body temperature and clock genes mRNA expression in the periphery and SCN. The alteration of the clock function, a new concept of adverse effects, was overcome by devising a dosing schedule that minimizes adverse drug effects on clock function. Furthermore, to produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules or several drugs appears to lead to the new concept of chronopharmacotherapy. One approach to increasing the efficiency of pharmacotherapy is administering drugs at times during which they are best tolerated. Finally, we developed the vector showing rhythmic gene expression for the intelligent chrono-drug delivery system.

哺乳动物的昼夜节律起搏器位于成对的视交叉上核（SCN）中。时钟基因是控制生理和行为昼夜节律的基因。许多药物的有效性和毒性取决于给药时间，而给药时间与生物钟控制下的生化、生理和行为过程的 24 小时节律相关。然而，许多药物的给药仍然不考虑一天中的时间。识别用于选择给药时间的节律标记将导致时间药物疗法的进展和扩散的改善。监测节律标记有助于选择一天中最合适的给药时间，以增加其治疗效果和/或减少其副作用。另一方面，一些药物可能会导致 24 小时节律改变，从而导致疾病和体内平衡调节改变。我们展示了干扰素对外周和视交叉上核的运动活动节律、体温和时钟基因 mRNA 表达的破坏作用。时钟功能的改变是不良反应的一个新概念，通过设计一个给药方案来克服，该方案可以最大限度地减少药物对时钟功能的不良影响。此外，通过使用改变的喂养计划或几种药物的节律性施用来操纵活器官的状况来产生新的节律性似乎导致了时间药物疗法的新概念。提高药物治疗效率的一种方法是在耐受性最佳的时间给药。最后，我们开发了用于智能计时药物输送系统的显示节律性基因表达的载体。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The molecular mechanism regulating 24-hr rhythm of CYP2E1 expression in the mouse liver.

调节小鼠肝脏 CYP2E1 表达 24 小时节律的分子机制。

DOI：
发表时间：
2008
期刊：
Hepatology (in press)
影响因子：
0
作者：
Matsunaga;N;et. al.
通讯作者：
et. al.

The molecular mechanism regulating 24-hr rhythm of CYP2E1 expression in the mouse liver (in press)

调控小鼠肝脏CYP2E1表达24小时节律的分子机制（出版中）

DOI：
发表时间：
2008
期刊：
Hepatology
影响因子：
13.5
作者：
Matsunaga;N.;Ikeda;M.;Takiguchi;T.;Koyanagi;S.;Ohdo;S.
通讯作者：
S.

Glucocorticoid regulation of 24-hour oscillation in interferon receptor gene expression in mouse liver

糖皮质激素对小鼠肝脏干扰素受体基因表达24小时振荡的调节

DOI：
发表时间：
2006
期刊：
Endocrinology 147・11
影响因子：
0
作者：
Koyanagi S;et al.
通讯作者：
et al.

Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes: A possible mechanism of chemotherapy-induced circadian rhythm disturbances

DOI：
10.1016/j.bcp.2008.01.011
发表时间：
2008-04-15
期刊：
BIOCHEMICAL PHARMACOLOGY
影响因子：
5.8
作者：
Terazonoa, Hideyuki;Hamdan, Ahmed;Ohdo, Shigehiro
通讯作者：
Ohdo, Shigehiro

Molecular basis for rhythmic expression of CYP3A4 in serum-shocked HepG2 cells

DOI：
10.1097/fpc.0b013e3282f12a61
发表时间：
2007-12
期刊：
Pharmacogenetics and Genomics
影响因子：
2.6
作者：
Takako Takiguchi;Miho Tomita;Naoya Matsunaga;Hiroo Nakagawa;S. Koyanagi;S. Ohdo
通讯作者：
Takako Takiguchi;Miho Tomita;Naoya Matsunaga;Hiroo Nakagawa;S. Koyanagi;S. Ohdo