普萘洛尔氧化的侧链与S-美芬妥英4'-羟化酶活性之间无相关性。

No correlation between side-chain of propranolol oxidation and S-mephenytoin 4'-hydroxylase activity.

作者信息

Xie H G, Xu Z H, Huang S L, Liu J H, Wu J X, Jiang C H, Zhou H H

机构信息

Pharmacogenetics Research Institute, Hunan Medical University, Changsha, China.

出版信息

Zhongguo Yao Li Xue Bao. 1997 May;18(3):216-8.

PMID:10072936

Abstract

AIM

To determine if any correlation between the side-chain oxidative capacity for propranolol and S-mephenytoin 4'-hydroxylase (cytochrome P-450 2C19, CYP2C19) activity in healthy Chinese of Han nationality.

METHODS

S-mephenytoin oxidative metabolite 4'-hydroxymephenytoin (4'OH-M), S- and R-mephenytoin, and naphthoxyl-actic acid (NLA) excreted in urine, and propranolol in plasma were measured after 14 healthy extensive metabolizers of S-mephenytoin oxidation were given a single oral dose of racemic mephenytoin 100 mg and racemic propranolol 80 mg, respectively. S/R-mephenytoin in urine was determined by chiral capillary gas chromatography with nitrogen-phosphorus detection, 4'-OH-M in urine by reversed-phase liquid chromatography (RPLC) with ultraviolet detection, and plasma propranolol or urinary NLA by the RPLC with fluorescence detection.

RESULTS

No significant correlations were found between the partial metabolic clearance (Clm) of propranolol to NLA and 8 h urinary S/R ratio of mephenytoin (rs = -0.0484; P = 0.8695), nor between the Clm and log10 of 8 h urinary excretion of 4'-OH-M (rs = -0.1077; P = 0.7140).

CONCLUSIONS

CYP2C19 is not a principal P-450 isozyme responsible for the in vivo side-chain oxidation of propranolol in the Chinese.

摘要

目的

确定汉族健康中国人中普萘洛尔侧链氧化能力与S-美芬妥因4'-羟化酶（细胞色素P-450 2C19，CYP2C19）活性之间是否存在相关性。

方法

14名S-美芬妥因氧化的健康强代谢者分别单次口服100 mg消旋美芬妥因和80 mg消旋普萘洛尔后，测定尿中排泄的S-美芬妥因氧化代谢产物4'-羟基美芬妥因（4'OH-M）、S-和R-美芬妥因以及萘氧基乳酸（NLA），以及血浆中的普萘洛尔。采用带氮磷检测的手性毛细管气相色谱法测定尿中的S/R-美芬妥因，采用带紫外检测的反相液相色谱法（RPLC）测定尿中的4'-OH-M，采用带荧光检测的RPLC测定血浆普萘洛尔或尿NLA。