Phase I study of TY-10721 ((Asp1-Ile5) angiotensin II).
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概要
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Angiotensin-II-Induced Hypertension Chemotherapy is an approach to selective enhancement of drug delivery to tumor tissue for increase of chemotherapeutic effects. TY-10721 (TY) is a newly synthesized compound of human type of angiotensin II ([Asp<SUP>1</SUP>-Ile<SUP>5</SUP>] angiotensin II) by TOA EIYO Ltd.(Tokyo).<BR>Along with and after stopping of the continuous infusion of TY, blood pressure and plasma concentration of angiotensin II, aldosterone, renin activity, and other biochemical parameters were measured in six healthy male volunteers.<BR>Using 2.5 and 5 μg/ml of TY, the mean arterial blood pressure (diast. BP+1/2 press. diff.) elevated to 138.7±8.9 mmHg (before, 85.7±7.0) in about 4 min after start of the infusion, and maintained the level of 144.1±8.3 mmHg. After stopping of TY, blood pressure immediately fell down to the previous level (87.0±4.9 mmHg) in 3-4 min.<BR>Plasma concentration of angiotensin II was 207.6±99.1 and 260.0±100.3 pg/ml during hypertension state compared with that of 23.2±8.3 (before) and 18.4±11.5 (30 min after).<BR>Half-life of TY in the plasma was 69.3±16.9 sec.<BR>Although elevation of blood pressure could be obtained by the infusion of TY, there was no proportional relation between the elevation level and the administrating doses. Response of elevation of blood pressure had individual variations.<BR>Significant rise of aldosterbfie and suppression of renin activity, though within the physiological deviation range, was observed. There were no particular changes in the plasma sodium and potassium level and in the'ECG monitoring.<BR>Phase II study of induced hypertension chemotherapy using TY is now under way.
- 一般社団法人 日本臨床薬理学会の論文
著者
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佐藤 春彦
東北大学抗酸菌病研究所臨床癌化学療法部門
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鈴木 磨郎
東北大学抗酸菌病研究所, 肺癌部門
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星 正彦
財団法人厚生会仙台厚生病院消化器科
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涌井 昭
東北大学抗酸菌病研究所臨床癌化学療法研究部門
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