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Published on: March 28, 2017
Effect of CYP2D6 polymorphisms on the pharmacokinetics of propafenone and its two main metabolites
Mohammad-Reza Rouini1, Minoo Afshar2
1Biopharmaceutics and pharmacokinetics division, department of pharmaceutics, faculty of pharmacy, Tehran university of medical sciences, P.O. Box 14155-6451, Tehran, Iran.
Aim Of The Study:
Propafenone (PPF) is an antiarrhythmic drug, metabolized mainly by CYP2D6 to 5-hydroxypropafenone (5OH-PPF) and by CYP3A4 to norpropafenone (NOR-PPF). CYP2D6 shows a high degree of genetic polymorphism which is associated with diminished antiarrhythmic efficacy or cardiac seizures/cardiotoxicity. This study aimed to investigate the effect of the CYP2D6 polymorphism on the pharmacokinetics of PPF and its two main metabolites. The usefulness of PPF/5OH-PPF ratio for CYP2D6 phenotyping in healthy adults was also evaluated.
Methods:
Twelve healthy volunteers, 3 poor metabolizers (PM), 2 intermediate metabolizers (IM) and seven extensive metabolizers (EM) received an oral dose of PPF. Concentrations of PPF and its metabolites were analyzed in serum samples over 27h.
Results:
The PPF/5OH-PPF ratio distinguished EMs from PMs, but not from IMs. In PMs, the mean transit time (MTT) values were almost the same for PPF and NOR-PPF and much higher than those of EMs and IMs. 5OH-PPF was not detected in EMs. Mean MTT values of 5OH-PPF and NOR-PPF in IMs were 5.27- and 1.52-fold higher than those of EMs.
Conclusion:
A single time point serum PPF-MR approach is a useful tool to identify PMs. CYP2D6 polymorphism significantly affects the pharmacokinetics of PPF and its two metabolites.
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