Pharmacokinetic and pharmacodynamic studies of anti-hypertensive agents and its interactions.
| Project/Area Number |
10672096
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Niigata College of Pharmacy |
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Principal Investigator |
SATO Shinji Niigata College of Pharmacy, Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (70211943)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Carvedilol / Norepinephrine / PK-PD analysis / Hypotensive effect / Blood pressure regulation / Spontaneous hypertension rats / 相互作用 / ベラパミル / カテコールアミン / ラット / ファーマコキネティクス / ファーマコダイナミクス / 降圧作用 / 薬物間相互作用 / 相加作用 / 相乗作用 |
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| Research Abstract |
It has been recognized that the blood pressure is always regulated by various blood pressure regulation systems. The treatment by the anti-hypertensive agents is required for the hypertensive patients who have the dysfunction of the blood pressure regulation systems. The establishment of the quantitative relationship between pharmacokinetics (PK) and pharmacodynamics (PD) of anti-hypertensive agents is very important to manage the optimal therapeutic response with the minimum adverse reactions. However, the enlargement of the plasma norepinephrine (NE) concentrations by the excitement of sympathetic nervous systems is induced by the hypotension after the administration of the anti-hypertensive agents. The purpose of the present study is to develop the PK-PD model for carvedilol (CVL) with the fluctuation of the plasma norepinephrine concentrations in the spontaneous hypertension rats, and to examine whether the constructed PK-PD model can be established the quantitative relationship be
… More
tween PK and PD of CVL.In order to construct PK-PD model with the excitement of sympathetic nervous systems, it is necessary to clarify the relationship between the pharmacokinetics and the hypertensive response of NE.The time course of plasma NE concentrations could be described by a two-compartment model included the linear and non-linear elimination kinetics, and the hypertensive response of NE could be described by the Emax model. The time courses of plasma CVL concentrations could be described by a two-compartment model with the linear elimination kinetics. The plasma NE concentrations during the infusion of CVL were increased with the enlargement of the infusion rates of CVL, and these time courses of the plasma NE concentrations could be described by the blood pressure regulation model in which the production rate for the endogenous plasma NE concentrations is increased by the decreasing of the blood pressure. The hypotensive effect of CVL could be described by the sigmoid Emax model which included the constructed blood pressure regulation model. Less
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Report
(3 results)
Research Products
(2 results)
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[Publications] Kenichi Watanabe, Yoshimi Ohta, Takahiro Kouda, Tomoyuki Sekiguchi, Shinji Sato, Mikio Nakazawa, Go Hasegawa, Makoto Naito, Koichi Fuse, Masahiro Ito, Satoru Hirono, Naohito Tanabe, Haruo Hanawa, Kiminori Kato, Makoto Kodama and Yoshifusa Aizawa: " Acute effects of endothelin-1 and TAK-044 (ETA and ETB receptor Antagonist) in rats with dilated cardiomyopathy."J.Cardiovasc.Pharmacol.. 36. S49-S54 (2000)
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