Sensitive radioreceptor assay of the calcium antagonist benidipine hydrochloride in plasma and urine.
Plasma and urinary concentrations of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) were measured by the radioreceptor assay using 3H-nitrendipine and rat cardiac membrane receptor. After methanol deproteinization and ethyl ether extraction under alkaline conditions as pretreatment, the detection limit for KW-3049 in plasma was 0.2 ng/ml using 0.5 ml of sample. For the urine, 0.05 ml of urine sample was directly added to the assay system, and detection limit of drug was 1 ng/ml. The cross-reactivity of the presumable metabolites was 1% or less of the unchanged drug. This radioreceptor technique was applied to pharmacokinetic studies and useful for monitoring the drug after therapeutic dosing.
Ishii
A
A
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Nishida
K
K
Oka
T
T
Nakamizo
N
N
D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D004285:Dogs; D008297:Male; D015394:Molecular Structure; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D009568:Nitrendipine / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D012044:Regression Analysis
D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D009568:Nitrendipine; D009543:Nifedipine