Nitrendipine (NTD), a newly developed calcium antagonist was administered to 12 Japanese healthy volunteers to evaluate its safety, pharmacokinetics and pharmacological properties.
Five, 10, and 20 mg of NTD and 10 mg of nifedipine (NFD) were orally administered to 6 subjects in single-dose study. NTD (10 mg) was administered to 6 subjects once a day for 7 days in multiple-dose study. Subjects complained of headache and dull headedness after administration of NTD and NFD in single-oral-dose study but there were no reported side effects in multiple-dose study.
Plasma concentration elevated more gradually after a single dose of NTD . Time to maximum plasma concentration and the elimination half-life were longer in NTD than in NFD. The time to maximum plasma concentration and the elimination half-life after multiple dosing were almost the same as those after first dosing . Unchanged NTD was not detected in any urine sample.
Blood pressure decreased and pulse rate increased after single administration of NTD and NFD. Blood pressure decreased more gradually after NTD than after NFD.
Plasma concentration of norepinephrine increased significantly after NFD but not after NTD. In multiple dosing, the exercise-induced elevation of plasma concentration of nore-pinephrine was inhibited significantly by NTD after the first dosing but not after the last dosing.
Plasma renin activity elevated after single administration of NTD and NFD. Plasma concentration of aldosterone did not change after single administration of NTD. In multiple dosing, plasma renin activity did not change significantly and plasma concentration of aldosterone decreased significantly.
These results suggested that NTD would be a safe and useful antihypertensive agent with long duration of action.