Ishii A, Nishida K, Oka T, Nakamizo N
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Arzneimittelforschung. 1988 Nov;38(11A):1733-7.
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.
采用³H-尼群地平与大鼠心肌膜受体，通过放射受体分析法测定了(±)-(R*)-2,6-二甲基-4-(间硝基苯基)-1,4-二氢吡啶-3,5-二羧酸(R*)-1-苄基-3-哌啶酯甲酯盐酸盐（盐酸贝尼地平，KW-3049）的血浆和尿液浓度。作为预处理，先进行甲醇脱蛋白及碱性条件下的乙醚萃取，使用0.5ml样品时，血浆中KW-3049的检测限为0.2ng/ml。对于尿液，将0.05ml尿液样品直接加入分析系统，药物检测限为1ng/ml。推测代谢产物的交叉反应性为未变化药物的1%或更低。这种放射受体技术应用于药代动力学研究，对治疗给药后监测药物很有用。
