CYP2D6 GENOTYPE AND PLASMA CONCENTRATIONS OF OLANZAPINE - IMPORTANCE FOR SAFETY IN BIOEQUIVALENCE STUDIES
Journal
Македонски медицински преглед = Macedonian medical review
Date Issued
2013
Author(s)
Abstract
Introduction. Functional status of izozymes CYP2D6
and CYP1A2 has a major impact on pharmacokinetics
of a number of psychotropic drugs. There are no definitive
data on the predictive role of these enzymes. Our
goal was to show, in our conditions, whether the disposition
of olanzapine is associated with the impact of polymorphisms
of CYP2D6 by deductive comparing the
pharmacokinetic results of a bioavailability study.
Methods. Blood samples were taken from healthy subjects
participating in studies of bioavailability, for genotyping
for the most common polymorphic allelic variants.
Gene duplication genotyping was performed at
the Faculty of Pharmacy using PCR technique. Concentrations
of olanzapine in plasma were assessed with
appropriate HPLC method.
Results. The most common allelic variants of CYP2D6
and their frequency were determined; subsequently 4
groups of phenotypes (EM, IM, PM and UM) were promoted.
For 14 subjects divided into 3 groups of phenotypes
Cmax, AUC0-t and AUC0-inf were determined. Despite
the apparent numerical differences in concentrations of
maximum plasma concentrations and the area under the
curve, there were no significant difference between the
groups (EM: IM, EM: UM). Adverse reactions were mild by nature and were expected
for the drug: headaches and dry mouth, which are
typical for antipsychotic drugs, especially for olanzapine
at a dosage of 10 mg.
Conclusions. Additional research has to be made to confirm
the impact of CYP2D6 allelic gene variants on the
pharmacokinetics of olanzapine. In future studies of
bioavailability, subjects with a certain phenotype must
be assesed with caution due to the potential possibility
of increased drug concentrations.
and CYP1A2 has a major impact on pharmacokinetics
of a number of psychotropic drugs. There are no definitive
data on the predictive role of these enzymes. Our
goal was to show, in our conditions, whether the disposition
of olanzapine is associated with the impact of polymorphisms
of CYP2D6 by deductive comparing the
pharmacokinetic results of a bioavailability study.
Methods. Blood samples were taken from healthy subjects
participating in studies of bioavailability, for genotyping
for the most common polymorphic allelic variants.
Gene duplication genotyping was performed at
the Faculty of Pharmacy using PCR technique. Concentrations
of olanzapine in plasma were assessed with
appropriate HPLC method.
Results. The most common allelic variants of CYP2D6
and their frequency were determined; subsequently 4
groups of phenotypes (EM, IM, PM and UM) were promoted.
For 14 subjects divided into 3 groups of phenotypes
Cmax, AUC0-t and AUC0-inf were determined. Despite
the apparent numerical differences in concentrations of
maximum plasma concentrations and the area under the
curve, there were no significant difference between the
groups (EM: IM, EM: UM). Adverse reactions were mild by nature and were expected
for the drug: headaches and dry mouth, which are
typical for antipsychotic drugs, especially for olanzapine
at a dosage of 10 mg.
Conclusions. Additional research has to be made to confirm
the impact of CYP2D6 allelic gene variants on the
pharmacokinetics of olanzapine. In future studies of
bioavailability, subjects with a certain phenotype must
be assesed with caution due to the potential possibility
of increased drug concentrations.
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