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