Probucol の高脂血症に対する用量の検討

II. 封筒法による多施設参加用量試験からみた単位有効量と有効反応率

抄録

To determine the optimal dose of probucol in Japanese, we conducted a multi-central cooperative study on two doses of 750mg and 1000mg a day. The two doses were randomly allocated to 112 subjects with hyperlipidemias from 11 centers, out of whom 7 were excluded from the study because they were unsuited for the protocol, and 5 dropped out. The rest 100 cases completed the study, 54 being on 750mg and 46 on 1000mg a day. Their fasting blood samples were collected to a central laboratory and determined for serum total cholesterol, triglycerides and HDL-cholesterol.
The effect of probucol was analysed in this study in terms of the unit dose effect and the rate of effective case in each group. The unit dose effects were for total cholesterol 4.5mg/dl/100mg (the unit omitted hereafter) from 750mg group and 4.0 from 1000mg group. For triglycerides 4.1 from 750mg and 2.7mg from 1000mg group. For HDL-cholesterol 1.0 from 750mg group and 0.8 from 1000mg group, respectively.
The rate of effective case was for total cholesterol 91% in 750mg group and 94% in 1000mg group, for triglycerides 67% in 750mg and 70% in 1000mg group, and for HDL-cholesterol 9% in 750mg group and 14% in 1000mg group, respectively.
These data indicated that probucol was more efficient in a daily dosis of 750mg in terms of the effect exerted by the unit amount of the drug, while it was more effective in 1000mg administration in terms of the numbers of cases whose unit dose effect became positive. Taking together, the magnitude of effects and the nature of drug, we considered that the unit dose effect was the more important determinant and that the daily dosis of 750mg was the favorable dose for use compared with 1000mg administration.