Pharmacokinetics of barnidipine hydrochloride, a new dihydropyridine calcium channel blocker, in the rat, dog and human.
1. The pharmacokinetics of a new calcium antagonist barnidipine hydrochloride, a stereochemically pure enantiomer, was studied after intravenous and oral dosing to the rat and dog, and oral to man. 2. After intravenous dosing, plasma concentrations of barnidipine hydrochloride declined bi-exponentially with the terminal half-lives of 0.6 h in the rat and 4.1 h in the dog. The blood clearance was 5.2 l/h/kg in the rat and 3.3 l/h/kg in the dog, and was comparable with hepatic blood flow in both species. 3. After oral dosing, plasma concentrations of barnidipine hydrochloride peaked rapidly (0.3-0.4 h in the rat and dog, 1.0-1.6 h in man). Cmax and AUC rose non-linearly with increasing doses in all three species. 4. The absolute bioavailability was low (11-18% in the rat and 6-9% in the dog), suggesting a marked first-pass metabolism.
Teramura
T
T
Drug Metabolism Department, Yamanouchi Pharmaceutical Co., Ltd, Tokyo, Japan.
Watanabe
T
T
Higuchi
S
S
Hashimoto
K
K
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D004285:Dogs; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D015394:Molecular Structure; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; C050699:mepirodipine; D009543:Nifedipine