Phase I study of carvedilol (DQ-2466), a new .BETA.-blocker. (The 1st report). The study in single oral administration.

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Carvedilol (DQ-2466) is a new β-blocker with vasodilating properties. In order to investigate the hemodynamics and safety of carvedilol after single oral administration, in a placebo controlled manner, each group of 5 healthy male volunteers was treated with ascending doses of 20, 40, or 60 mg. The following results were obtained: (1) Both systolic and diastolic blood pressures at rest decreased significantly from 2 hr to 24 hr after administration of carvedilol at each dose level (P<0.05-0.001). Maximum decreases of systolic and diastolic blood pressures were achieved at 3-4 hr after administration. The changes of systolic blood pressure (SBP Δ%) were 4. 2, 14. 6, 16. 2, and 16. 6% in placebo, 20, 40, and 60 mg group, respectively, at 3 hr after dosing. The changes of diastolic blood pressure (DBP Δ%) were 0.5, 16. 1, 13. 3, and 18. 8% in placebo, 20, 40, and 60 mg group, respectively, at 4 hr after dosing. There was no significant difference in the changes of pulse rate (PR Δ%) at rest between carvedilol administration group and placebo admistration group.(2) Stroke index (SI) and cardiac index (CI), which were determined by echocardiography, were not affected in the 20 mg group.SI and CI slightly decreased in the 40 mg group in comparison with the placebo group.There was a tendency of decrease in these parameters in the 60 mg group.Total peripheral vascular resistance (TPVR) decreased significantly at 4 and 29 hr after 20 mg dosing.(3) The increase of systolic blood pressure on treadmill exercise was significantly reduced with dose-dependency in carvedilol administration groups for 9 hr after dosing.(4) There were no abnormal laboratory findings. No subjective symptoms were observed in the placebo and the 20 mg group.One of 5 subjects in the 40 mg group 4 of 5 subjects in the 60 mg group showed slight dizzy feeling, heavy-headedness, nausea, and dizziness.(5) In conclusion, carvedilol appears to maintain marked hypotensive effects up to 24 hr after single oral administration of 20 mg, which was the lowest dose in this study. At less than 40 mg, there were no clinically significant subjective symptoms. This suggests that maximum daily dose should be less than 40 mg in the future investigation for multiple dosing.
一般社団法人日本臨床薬理学会の論文

Phase I study of carvedilol (DQ-2466), a new .BETA.-blocker. (The 1st report). The study in single oral administration.

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