Abstract
A newly developed calcium antagonist, FK 235, was orally administered to 16 healthy male volunteers in a single-dose and a 7 multiple-dose trial to investigate the pharmacokinetics and pharmacodynamics of this drug.
1. Single-dose trial
Clinical symptoms were encountered in subjects given 1mg or more, ascribed to dilatation of the peripheral blood vessels. FK 235 caused no clear effect on systolic blood pressure, but a dose-dependent decrease of diastolic blood pressure and increase of pulse rate after dosing with 2mg or more were seen.
FK 235 inhibited rise in total peripheral resistance in cold pressor test, and increased cardiac index at rest.
The area under the curve (AUC) after dosing with 8 mg was 25.6 ng·hr/ml and the elimination half-life was 1.4 hrs.
FK 235 had no effect on laboratory test values or ECG findings.
2. Multiple-dose trial
There were on other clinical symptoms except transient facial flush in one subject on the 2nd day.
Systolic blood pressure after dosing was not significantly lower than on the observation day, but diastolic blood pressure was significantly lower.
There were no abnormal laboratory test findings except an increase of transaminase in 2 subjects.
