1990 Volume 21 Issue 4 Pages 691-702
The relationship between the plasma concentration and the hypotensive effect of DHP-218 after a single oral administration was investigated in 5 inpatients with essential hypertension. And, at the same time, a pre-pilot study of DHP-218 in essential hypertension was conducted in 20 patients using fixed and flexible dose method. Starting with the initial dose of 0.5mg twice daily, the dosage was raised with a two-fold increase considering the effect and the tolerance of patients. The following findings were obtained from the studies.
1. The time course of plasma concentration of DHP-218 after a single oral administration to patients with essential hypertension was found to be almost the same as the result obtained in the phase I study.
2. The hypotensive effect of DHP-218 was parallel with the changes of the plasma concentration, and the effect lasted for 12 hr.
3. A significant decrease of blood pressure was observed at the dose of 1mg/day. From the evaluation of the hypotensive effect, a moderate or more-than-moderate decrease of blood pressure was observed in 18 out of the 20 cases at the maximum.
4. The hypotensive effect of DHP-218 was found to be dose-dependent: i. e., the cumulative percentages of hypotensive effect were 20%, 50%, 75%, and 90% at 1mg, 2mg, 4mg, and 8 mg/day, respectively.
5. Four cases experienced side effects including headache and facial hot flush, which were regarded as typical adverse reactions of calcium antagonists. None of them required dose reduction or discontinuation of the drug and none were considered to be of any safety problem.
6. There were no changes in laboratory test findings after administration of DHP-218. The above findings suggested that DHP-218 can be expected to be a clinically useful antihypertensive drug having a long-lasting effect at low dosage level.
