Premium
Effect of quinidine on the dextromethorphan O‐demethylase activity of microsomal fractions from human liver.
Author(s) -
Broly F,
Libersa C,
Lhermitte M,
Bechtel P,
Dupuis B
Publication year - 1989
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1989.tb03502.x
Subject(s) - dextromethorphan , quinidine , microsome , chemistry , debrisoquine , dextrorphan , microsoma , enzyme , michaelis–menten kinetics , pharmacology , cyp2d6 , cytochrome p450 , biochemistry , enzyme assay , biology
1. The kinetics of dextromethorphan O‐demethylation were measured in microsomes prepared from five human livers, both in the absence and in the presence of quinidine. 2. For each liver and over the concentration range of dextromethorphan examined (4.2‐3400 microM), this reaction involved an enzymatic component of high affinity, with an apparent Michaelis‐Menten constant (Km) of 4.6 +/‐ 1.8 microM (mean +/‐ s.d.) and a maximum velocity (Vmax) of 4.2 +/‐ 3.5 nmol mg‐1 h‐1 (mean +/‐ s.d.). 3. Quinidine was a potent and competitive inhibitor of the activity of this component (mean Ki +/‐ s.d. of 0.025 +/‐ 0.008 microM) as it is for other oxidation reactions which have already been found to co‐segregate with the debrisoquine‐type polymorphism. 4. With microsomes from four of the five livers studied, there was evidence of a second enzymatic component of activity characterized by a similar Vmax and about 20‐fold higher Km compared with the high affinity component. The activity of this low affinity component was unaffected by quinidine in the concentrations studied.