METABOLIC-FATE OF FELODIPINE IN MAN - IN SEARCH OF NEW DIHYDROPYRIDINE METABOLITES

被引：5

作者：

OHTAKE, Y

SAKAMOTO, T

NISHIOKA, R

UNO, K

TABATA, S

机构：

[1] Laboratory for Galenics, Pharma Research Laboratories, Hoechst Japan Limited, Kawagoe, Saitama, 350, 3-2

[2] Sumika Chemical Analysis Service Limited, Osaka

[3] Pharmacokinetic Research Laboratory, Ciba-Geigy (Japan) Limited, Takarazuka, Hyogo

来源：

DRUG INVESTIGATION | 1992年 / 4卷 / 06期

关键词：

D O I：

10.1007/BF03259219

中图分类号：

R9 [药学];

学科分类号：

1007 [药学];

摘要：

A new metabolic pathway for felodipine was confirmed by identification and quantification of new felodipine metabolites retaining the dihydropyridine structure. Following administration of a 10 mg dose to 6 healthy subjects, felodipine was rapidly absorbed, reaching maximum concentration (C(max)) [22.5 ng/ml] after 1.5 hours, and was then eliminated with a half-life of 3.1 hours. The pyridine metabolite had a similar plasma concentration-time course to that of the parent compound, with a C(max) of 30.1 ng/ml and an elimination half-life of 2.8 hours. In contrast, the dihydropyridine metabolite (5-carboxy derivative) reached a C(max) value (47.8 ng/ml) 1.9 hours after administration and was eliminated with a half-life of 8.1 hours. This plasma dihydropyridine metabolite was identified by GC-MS (GC-mass spectrometry) in comparison with the standard material. The dihydropyridine metabolite was not detectable in urine. These results suggest that in contrast to current beliefs, felodipine is metabolised via ester hydrolysis with the dihydropyridine ring retained.

引用

页码：528 / 534

页数：7

共 17 条

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