Valproic acid (2-propylpentanoic acid) is an anticonvulsant drug, widely used in the treatment of epilepsy, affecting both children and adults (1, 2). It is also used to treat bipolar disorder and to prevent migraine headaches (3).Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is used in clinical practice to aid the treatment of patients with epilepsy. In order to obtain information A bioanalytical HPLC method with UV detection for the determination of the antiepileptic drug valproic acid in human saliva has been developed and validated. Saliva represents an alternative matrix for therapeutic monitoring of antiepileptic drugs due to the increasing interest in free drug concentration. The proposed method involved solid-phase extraction for sample preparation and yielded very good mean recoveries of 99.4 % and 97.9 % for valproic acid and IS, respectively. The calibration function for valproic acid was linear over the concentration range of 1.0-50.0 mg mL -1 (R 2 = 0.9989). Within-run and between-run precision and accuracy were studied at four concentrations and RSDs were less than 7.3 and 2.2 %, while accuracy values were higher than 96.8 and 97.5 %, respectively. The described method provides sensitivity, linearity, precision, accuracy and is suitable for analyses of valproic acid in saliva samples.
Patients and methodsA sample of breast cancer patients (n=62 women) were interviewed for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in Albanian. Reliability of the questionnaire was considered acceptable if Cronbach’s alpha was ≥0.70. Item convergent-discriminant validity was tested through multitrait scaling analysis. Construct validity was tested under the hypotheses that QLQ-C30 interscale correlations would have an acceptable value of ≥0.40 and as well as by known group comparisons assessing differences of patient subgroups with reference to disease stage and education level.ResultsThe mean age of the patients was 50 years (standard deviation: 10.9 years). Cronbach’s alpha ranged from 0.54 for the cognitive functioning scale to 0.96 for the global health quality of life (GH/QoL) scale. In multitrait scaling analysis, the strength of Spearman’s correlations between an item and its own subscale was ≥0.40, with the exception of item 5 (ρ=0.22); results for item discriminant validity were satisfactory, with the exception of item 5, which showed higher correlation with other subscales than with its own physical functioning. The Spearman’s interscale coefficients generally were correlated with each other. Results of known group comparisons did not show significant differences in terms of disease stage. Regarding education level, patients with high school/university education had better functional scales scores only in certain subscales compared to other subgroups; furthermore, patients with secondary school education had better GH/QoL compared to other subgroups of patients.ConclusionThe EORTC QLQ-C30 (v3.0) in Albanian was found to be valid and reliable for women with breast cancer and could be considered as a starting point for further evaluation study.
Genetic variation in the regulation, expression and activity of genes coding for Phase I, Phase II drug metabolizing enzymes (DMEs) and drug targets, can be defining factors for the variability in both the effectiveness and occurrence of drug therapy side effects. Information regarding the geographic structure and multi-ethnic distribution of clinically relevant genetic variations is becoming increasingly useful for improving drug therapy and explaining inter-individual and inter-ethnic differences in drug response.This study summarizes our current knowledge about the frequency distribution of the most common allelic variants in three broad gene categories: the Phase I oxidation-cytochrome P450 (CYP450) family (CYP2C9, CYP2C19, CYP3A5, CYP2D6); the Phase II conjugation (GSTT1, SULT1A1; UGT1A1) and drug target (TYMS-TSER, MTHFR and VKORC1) in the population of the Republic of Macedonia and compares the information obtained with data published for other indigenous European populations.Our findings define the population of the Republic of Macedonia as an ethnic group with a highly polymorphic genetic profile. These results add to the evidence regarding the distribution of clinically important variant alleles in DME and drug target genes in populations of European ancestry.
The aim of this study was to evaluate the most common ABCB1 (MDR1, P-glycoprotein) polymorphisms in the population of R. Macedonia and compare the allele and haplotype frequencies with the global geographic data reported from different ethnic populations. The total of 107 healthy Macedonian individuals from the general population was included. Genotypes for the ABCB1 for three polymorphisms C1236T [rs1128503], G2677A/T [rs2032582] and C3435T [rs1045642] were analyzed by Real-Time PCR. Obtained allele frequencies for these three SNPs were similar to those observed in other European Caucasians. The detected genotype frequencies were 33.6% for 1236CC, 44.9% for 1236CT and 21.5% for 1236TT in exon 12; 32.7%, 44.9% and 22.4% for 2677GG, 2677GT and 2677GT consecutively in exon 21; and 25.2% for 3435CC, 52.3% for 3435CT and 22.5% for 3435TT in exon 26.Strong LD was observed in our study among all = 0.859, r 2 = 0.711). Eight different haplotypes were identified and the most prominent was the CGC haplotype (45.3%). Our study was the first to have documented the distribution of ABCB1 alleles, genotypes and haplotypes in the population of R. Macedonia. The obtained results can help in the prediction of different response to the drugs that are P-glycoprotein substrates. Additionally, in the era of individualized medicine the determination of the P-glycoprotein genotype might be a good predictive marker for determination of the subpopulations with higher risk to certain diseases.
Carbamazepine (CBZ) blocks neuronal sodium channels in a voltage- and frequency-dependent manner, delaying the recovery of the channels from the inactivated state, reducing the number of action potentials within a burst, and decreasing burst duration. The α-subunit of the first neuronal sodium channel (SCN1A) is a major gene in different epilepsies. A synonymous polymorphism (SCN1A IVS5N + 5 G>A or rs3812718) is common in exon 5 of this gene. Mutations in the α-unit of this gene are associated with CBZ-resistant epilepsy and a higher maintenance dose of CBZ. We have investigated the association of this single nucleotide polymorphism (SNP) and epilepsy, efficacy and dose-dependence of CBZ therapy in 147 adult Macedonian patients and 137 non epileptic controls. No significant differences in allelic frequencies and genotype distribution were found between patients and controls (p = 0.94278), or between CBZ-responsive and unresponsive patients (p = 0.55449). An association between the A allele and a higher maintenance dose in CBZ-responsive patients was detected. No statistical difference was found between the plasma levels of CBZ and genotype of patients receiving the same dose, indicating that the variant exerts its effect at the level of receptor responsiveness. The predictive value of pretreatment testing showed a minor insignificant difference between patients with different genotypes, primarily due to a small number of patients.
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