Search

Background: Distribution of CYP2C9 and VKORC1 gene polymorphisms may vary significantly among different ethnic groups, and eventually influence the variation in drug metabolism or even failure.Objective: The aim of this study was to evaluate the prevalence of CYP2C9 and VKORC1 alleles in the healthy population of Republic of Macedonia compared to the global geographic data reported from different ethnic populations. Also, to genotype CYP2C9 and VKORC1 genes and eventually to divide individuals in poor, extensive, or intermediate metabolizer.Material and Methods: Blood samples were collected after signing written consent, DNA was isolated from peripheral blood, and CYP2C9 and VKORC1 genes were typed (n=124). Genotyping was performed by commercially available kits (GeneID GmbH, Strassberg, Germany, AID Diagnostica), based on the method of polymerase chain reaction with a subsequent hybridization. The population genetics analysis package, PyPop ver. 0.6.0, was used for analysis of the data.Results: The frequency of alleles varies from 0.931 for CYP2C9*3 to 0.109 for CYP2C9*2 indicating common “wild type” allele in those genes. The frequency ranges spanned ~50% for each allele of VKORC1 gene, indicating no common “wild type” allele in this gene. Test of neutrality showed significant negative value for VKORC1 polymorphism that indicates balancing selection operating on the alleles at that locus. All polymorphisms of CYP2C9*2, CYP2C9*3 and VKORC1 showed a good fit with Hardy-Weinberg expectations.Conclusion: The results of polymorphic alleles of CYP2C9 and VKORC1 genes in Macedonian population can be used for the variation in drug metabolism studies as well for adapting dosage regimes for oral anticoagulant therapies.

BACKGROUND: The aim of this study is estimation of pharmacokinetic parameters: Cmax, tmax, t1/2, AUC0-t and AUC0-∞ with the two-way analysis of variance, single observation (ANOVA) for two preparations containing acyclovir.OBJECTIVE: In order to evaluate pharmacokinetic study of acyclovir, method for quantitative determination of acyclovir in human plasma should be simple, rapid and reproducible. Therefore, the method is developed, validated and applied for analysis of acyclovir in plasma samples obtained from healthy volunteers.MATERIAL AND METHODS: High performance liquid chromatographic (HPLC) method with UV-detection for the determination of acyclovir in human plasma is presented. This method involves protein precipitation with 20 % (V/V) perchloric acid. The chromatographic separation was accomplished on a reversed phase C8 column with a mobile phase composed of 0.1 % (v/v) triethylamine in water (pH 2.5). No internal standard is required. UV detection was set at 255 nm. The method was successfully applied for the evaluation of pharmacokinetic profiles of acyclovir tablets in 24 healthy volunteers.RESULTS: The validation results shows that proposed method is rugged, precise (RSDs for intra- and inter-day precision ranged from 1.02 to 8.37 %) and accurate (relative errors are less than 6.66 %). The calibration curve was linear in the concentration range of 0.1-2.0 µg/ml and the limit of quantification was 0.1 µg/ml. The Cmax, tmax and AUCs for the two products were not statistically different (p>0.05), suggesting that the plasma profiles generated by Zovirax were comparable to those produced by acyclovir manufactured by Jaka 80 company.CONCLUSION: Good precision, accuracy, simplicity, sensitivity and shorter time of analysis of the method makes it particularly useful for processing of multiple samples in a limited period of time for pharmacokinetic study of acyclovir.