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No correlation between side-chain of propranolol oxidation and S-mephenytoin 4'-hydroxylase activity
1Pharmacogenetics Research Institute, Hunan Medical University, Changsha, China.
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.