新しいＣａきっ抗薬，ＭＰＣ‐１３０４の健常人における薬理作用と薬物動態 １回経口投与の成績

Abstract

The pharmacodynamic and pharmacological effects of MPC-1304 after multiple oral administration were studied in a cross-over double-blind fashion with sustained release formulation of nifedipine (10 mg Sepamit® capsule) as reference drug, using 16 healthy adult male volunteers. They received 10 mg of MPC-1304 (once or twice a day) and 20 mg of nifedipine (twice a day) for 7 days.Pharmacokinetics of MPC-1304 were assessed by measuring plasma and urine concentrations of MPC-1304 itself and its metabolites. After multiple administration of MPC-1304, plasma concentrations of MPC-1304 itself and MPC-1304-keto-H2, the active metabolite, reached its plateau in 2 days and remained stable during the rest of the study.The calculated pharmacokinetic parameters on the seventh day were almost the same as those on the first day and were not so different from those of the single-dose study.The percent excretion ratio of MPC-1304 and its metabolites in 24-hr urine was not affected by multiple administration.These results suggested that neither accumulation nor significant change of pharmacokinetics was observed in the plasma levels of metabolites even after multiple administration of MPC-1304.Blood pressure did not change significantly both after MPC-1304 and nifedipine, though heart rate was transiently increased.Following multiple administration of MPC-1304 and nifedipine, subjects complained of headache and dull-headedness but all of these were transient and tolerable. Notable abnormalities were not observed in laboratory findings during the study and so there was not significant difference for adverse effects between two drugs.In conclusion, MPC-1304 can be expected to be a safe calcium channel blocker with hypotensive effect.