普萘洛尔侧链氧化与S-美芬妥英羟化酶活性间无相关(英文)

目的:了解健康志愿者S-美芬妥英(S-Mep)羟化酶(CYP2C19)与体内普萘洛尔(Pro)侧链氧化能力间的相关性.方法:14名健康的S-Mep强氧化代谢者分批分别口服单剂量消旋Mep 100 mg和消旋Pro 80 mg,分别用气相色谱和液相色谱方法定量分析人尿中S-和R-Mep、4＇-羟基美芬妥英(4＇-OH-M)、萘氧乳酸和人血浆中Pro的浓度.结果:0-8小时尿排泄的S/R比值和4＇-OH-M的1g D％均与Pro侧链氧化的部分代谢清除率不相关(r_s分别为-0.0484和-0.1077).结论:人的CYP2C19不是催化Pro侧链氧化代谢的主要的P-450酶.

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

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.