Pharmacokinetics and Safety of NZ-105 in Healthy Volunteers: Single-Dose and Multiple-Dose Studies.

Abstract

The newly developed calcium channel blocker, NZ-105, was orally administered to 26 healthy adult male volunteers in single-dose (10, 20, 40mg) and multiple-dose (40mg b. i. d.) studies to investigate the safety and pharmacodynamics and pharmacological properties. The following results were obtained. 1. Subjective symptoms were reported for the 20mg and 40mg single-dose and the multiple-dose studies, although these conditions were mild and transient. There were no abnormal findings in clinical laboratory tests. 2. A reduction in systolic and diastolic blood pressures was observed after the single administration of 20mg and 40mg doses of NZ-105. The maximum reduction was attained about 3 to 6hr after drug administration. Pulse rate increased along with the reduction in blood pressure. The multiple-dose study showed a stable and continued reduction in systolic and diastolic blood pressures. 3. NZ-105 showed a stable diuretic effect in the single-dose and the multiple-dose studies. 4. The maximum plasma concentration (C_max) and the area under the blood concentration vs. the time curve (AUC) were dose-dependent in the single-dose study. The AUC at day 1 and day 7 in the multiple-dose study was 52.8ng·hr/ml and 60.1ng·hr/ml, respectively. It is thus concluded that NZ-105 has no drug accumulation ascribable to the multiple dosing.