Circadian rhythm of drug actions : Application to the rational drug therapy in the aged.
| Project/Area Number |
02670091
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Oita Medical University |
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Principal Investigator |
NAKANO Sigeyuki Professor and chairman, Department of Clinical Pharmacology and Therapeutics, Oita Medical University, 医学部, 教授 (10033341)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | circadian rhythm / chronopharmacology / pharmacokinetics / gentamicin / amikacin / lithium / aging / aged person / 薬物クリアランス |
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| Research Abstract |
In the present study the effects of gentamicin, amikacin and lithium on the pharmacokinetics, drug effects and toxicity were studied in mice and rats from the chronobiological point of view. These drugs are the typical drugs which are not metabolized in the body but are mainly eliminated through the kidney into urine. In addition, the aging effects on the circadian rhythm of gentamicin clearance were explored in young and aged rats.
Main results obtained were as follows :
(1) There were the significant circadian rhythms in pharmacokinetics of these three drugs tested, showing higher clearance during the active phase (dark period) and lower clearance during the rest phase (light period).
(2) There were similar circadian rhythms in the toxicity and the efficacy of the drugs. Antimicrobial efficacy of amikacin against intraperitoneal infection with Psedomonas aeruginosa showed a significant circadian rhythm in mice, showing higher LD50 values during the active phase and lower LD50 values during the rest phase.
(3) Aging decreased the gentamicin clearance and diminished the circadian rhythm of gentamicin clearance by altering the rhythm characteristics of motor activities and food & water intake in rats.
Although further studies are necessary to clarify the relationship between the results obtained in animals at the present study and the rational drug therapy in clinical practice, the results provide very useful information to achieve the rational drug therapy, especially in the aged patients.
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Report
(3 results)
Research Products
(10 results)
