Absorption, metabolism and excretion after oral administration of a new Ca antagonist, 14C-benidipine hydrochloride to man

Abstract

1. In healthy male volunteers, the absorption, metabolite profiles and excretion of Cbenidipine hydrochloride, a new Ca antagonist, were investigated after oral administration at a dose of 8 mg. 2. C-benidipine hydrochloride was rapidly absorbed, and the plasma concentration of radioactivity and unchanged drug reached a maximum of 71 2 ng eq. ml at 1 1 h and 2 56 ng ml at 0 6 h respectively, and then declined bi-exponentially. The half-life in the elimination phase was 14 7 and 5 3 h respectively. AUC of unchanged drug was low, about 1% of that of radioactivity. 3. Five days after administration,36 4% of the administered radioactivity was excreted in urine and 58 9% in faeces. 4. The metabolite profiles in plasma, urine and faeces were analysed by hplc. At 1 h after administration the predominant metabolites in plasma were M9 and M2, which accounted for 13 8 and 8 2% of the radioactivity respectively, whereas unchanged drug represented 1 2%. Predominant metabolites in urine 12 h after administration were M3 andM8,whichaccountedfor2 22and2 21%oftheadministeredradioactivityrespectively. Metabolites excreted in faeces 120 h after administration were very complex and poorly separated by hplc and could not be characterized: unchanged drug was not detected in the faeces.