The effect of diltiazem pretreatment on the pharmacokinetics and pharmacodynamics of MPC-1304, a new calcium channel blocker, were evaluated in six healthy male volunteers. Placebo or diltiazem 60 mg was given orally three times daily for 3 days in a double-blind crossover method. MPC-1304 10 mg was administered orally two times at an interval of four weeks as a washout period. Diltiazem significantly increased the maximum plasma level (Cmax) and the area under the plasma concentration-time curve (AUC) of MPC-1304 from control values (3.0 +/- 1.5 to 10.2 +/- 4.8 ng/ml, p less than 0.05, and 11.0 +/- 3.8 to 36.0 +/- 15.6 ng.h/ml, p less than 0.01, respectively) without any changes of t1/2. In the case of the major active metabolite, side chain reduced form (MI), Cmax, AUC, and t1/2 were significantly increased by diltiazem as follows: Cmax, 60.7 +/- 21.1 to 171.4 +/- 73.6 ng/ml, p less than 0.05; AUC, 317.6 +/- 62.6 to 1,334.9 +/- 563.6 ng.h/ml, p less than 0.01; t1/2, 2.8 +/- 0.7 to 3.9 +/- 0.6 h, p less than 0.01. Diltiazem pretreatment slightly, but not significantly decreased blood pressure after MPC-1304 dosing. The inhibition of hepatic metabolism on MPC-1304 may explain the significant changes in pharmacokinetics of MPC-1304 after diltiazem pretreatment.