Absorption, metabolism and excretion after oral administration of a new Ca antagonist, 14C-benidipine hydrochloride to man.
1. In healthy male volunteers, the absorption, metabolite profiles and excretion of 14C-benidipine hydrochloride, a new Ca antagonist, were investigated after oral administration at a dose of 8 mg. 2. 14C-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 and M8, which accounted for 2.22 and 2.21% of the administered 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.
Kobayashi
H
H
Analytical and Pharmacokinetic Department, Kyowa Hakko Kogyo Co., Ltd., Shizudka, Japan.
Kobayashi
S
S
Dalrymple
P D
PD
Wood
S G
SG
Chasseaud
L F
LF
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000493:pharmacokinetics*; D004563:Electrochemistry; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D011485:Protein Binding
D001798:Blood Proteins; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C061004:benidipine