Absorption, metabolism and excretion after oral administration of a new Ca antagonist,

1. In healthy male volunteers, the absorption, metabolite pro® les 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 pro® les 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 and M8,which accounted for 2± 22 and 2± 21% oftheadministered radioactivity respectively. 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.