Effect of diltiazem on the pharmacokinetics of MPC-1304, a new calcium channel blocker.
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.
Ohashi
K
K
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Sudo
T
T
Sakamoto
K
K
Tateishi
T
T
Fujimura
A
A
Kumagai
Y
Y
Shiga
T
T
Ebihara
A
A
D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C059427:aranidipine; D004110:Diltiazem