Bocsan Ioana Corina 1, Major Zoltan 1, Maier Codruţa 3, Pop Radu 2, Iuga Cristina 3, Trifa Adrian 2,
Militaru Florentina Claudia 1, Buzoianu Anca Dana 1
1 Department of Clinical Pharmacology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
2 Department of Genetics, Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
3 Department of Drug Analysing, Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Abstract
The present study oversees the influence of CYP polymorphisms on the metabolism of VPA and the correlation between the genotype and the plasma levels. Materials and method. 46 patients either with idiopathic or secondary epilepsy, with a mean age of 37,37 ± 1,87, evaluated in the Neurology Clinic of Cluj-Napoca were included. All patients were under stable VPA treatment for at least a month. Steady state plasma concentrations were determined using the GC/FID technique. We considered therapeutic level between 50-100 μg/mL. Using the PCR-RFLP method for each patient we’ve determined allelic variant of CYP2C192 and CYP2C193. Results. 65% of the patients had therapeutic level of valproic acid, 15% supra-therapeutic and 20% sub-therapeutic level of it. 23,91% of the patients were heterozygous for CYP2C92 and 19,57% CYP2C92 for CYP2C93. Regarding CYP2C192 15,22% were heterozygous and 8.70% homozygous. Allele CYP2C19*3 was absent. There were no significant correlation established between the genetic metabolizer status and it’s phenotypic expression represented by the plasma concentrations. Conclusions. The metabolizer status defined by the different allelic expression of CYP2C9 and CYP2C19 doesn’t present statistically significant influences on VPA steady-state plasma concentrations.