Jakjovski, Krume
Preferred name
Jakjovski, Krume
Official Name
Jakjovski, Krume
Main Affiliation
Email
krume.jakjovski@medf.ukim.edu.mk
32 results
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Item type:Publication, Distribution of CYP2C9 and VKORC1 Gene Polymorphisms in Healthy Macedonian Male Population(ID Design 2012/Scientific Foundation SPIROSKI, 2013-12-15); ; ; - Some of the metrics are blocked by yourconsent settings
Item type:Publication, A New Solid-Phase Extraction Method for Determination of Pantoprazole in Human Plasma Using High-Performance Liquid Chromatography(ID Design 2012/Scientific Foundation SPIROSKI, 2019-06-15); ; ; ; A new simple, selective and accurate high-performance liquid chromatographic (HPLC) method utilising solid-phase extraction for the determination of pantoprazole in human plasma samples has been developed. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Distribution of the most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia(Walter de Gruyter GmbH, 2014-12); - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Comparative, single-dose bioavailability study of two 500 mg clarithromycin tablet formulations in healthy volunteers under fasting condition(Macedonian Pharmaceutical Society, 2019); ; ; ; Clarithromycin is a semi-synthetic macrolide antibiotic, chemically 6-0- methylerythromycin, formulated as immediate-release tablets, extended-release tablets, and granules for oral suspension. The objective of this study was to evaluate and compare the relative bioavailability, and therefore the bioequivalence of Clarithromycin 500 mg test formulation versus a reference Klacid® forte 500 mg formulation, following a single dose administration under fasting conditions. The study was a single center, open, single dose, randomized, two-way crossover study in healthy male volunteers, with a wash-out period of one week between study periods. Twenty-four male healthy volunteers, aged 18-49 years were included into study. Blood samples for determination of clarithromycin and 14-OH clarithromycin concentrations were withdrawn at zero (pre-drug administration), 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 and 36 hours post-drug administration. The determination of clarithromycin and 14-OH clarithromycin concentrations in plasma was performed using validated LC/MS/MS method and internal standardization after liquid/liquid extraction with methyl t-butyl ether. The test formulation of clarithromycin, dosed at 500 mg is bioequivalent for primary clarithromycin and 14-OH clarithromycin parameters (Cmax, AUC0-t and AUC0-∞) to the reference formulation after a single oral administration of 500 mg clarithromycin. Both medications were well tolerated with no serious adverse events. Thus, in view of the clinical use, both formulations are exchangeable without restrictions. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Comparative, Single-Dose, 2-Way Cross-Over Bioavailability Study of Two Olanzapine 10 Mg Tablet Formulations in Healthy Volunteers Under Fasting Conditions(Macedonian Academy of Sciences and Arts/Walter de Gruyter GmbH, 2022-07-13); ; ; ; Objectives: Olanzapine is an atypical antipsychotic that is approved across Europe, the USA, and in many other countries for oral treatment of schizophrenia and acute manic episodes in patients with bipolar disorder as well as for maintenance therapy to prevent recurrence in responders. The objective of the present study was to compare the pharmacokinetics of two 10 mg tablet formulations of Olanzapine following a single oral dose in healthy volunteers under fasting conditions, as per the European Medicine Agency (EMA) guidelines to grant marketing authorization. Methods: This study was a randomized, open-label, two-treatment, two-period, two-sequences, single-dose, cross-over design with a washout period of 14 days. Both the test and the reference products were administered as 10 mg tablets with 240 mL of water after an overnight fast in each study period. A total of twenty blood samples were collected before dosing and within 144 hours after drug administration. Adverse events were monitored, recorded, and evaluated by investigators throughout the study. Results: Of the 24 healthy adult male subjects enrolled, all of them completed both study periods. The geometric mean ratio 90% confidence intervals (CI) for fasting Cmax, AUC0-t, and AUC0-infinity were 94.83-113.71%, 95.04-105.69% and 95.94-107.00%, respectively. The 90% CI for the ratios of the three primary pharmacokinetic parameters (using log-transformed data) were within the range of 80-125%, meeting the regulatory criteria for bioequivalence. Conclusions: The generic Olanzapine was bioequivalent to the reference formulation. It was well tolerated and provides an acceptable alternative to the reference drug. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Acute fulminant hepatatis in kidney transplant recipient after repeated sevoflurane anesthesia--a case report and literature review(Bentham Science Publishers Ltd., 2013-04); ; ; Dohchev, SasoA liver dysfunction induced by halogenated volatile anaesthetics is considered as a significant diagnostic problem. The aim of our report was to describe the first case of lethal hepatic failure in a female patient undergoing kidney transplantation (KTx) from a living donor after repeated sevoflurane anaesthesia. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, AKR1D1*36 C>T (rs1872930) allelic variant is associated with variability of the CYP2C9 genotype predicted pharmacokinetics of ibuprofen enantiomers - a pilot study in healthy volunteers(Walter de Gruyter GmbH, 2019-09-01); ; ; ; Geskovska, Nadica MatevskaThe relative contribution of CYP2C9 allelic variants to the pharmacokinetics (PK) of ibuprofen (IBP) enantiomers has been studied extensively, but the potential clinical benefit of pharmacogenetically guided IBP treatment is not evident yet. The role of AKR1D1*36C>T (rs 1872930) allelic variant in interindividual variability of CYP450 mediated drug metabolism was recently elucidated. A total of 27 healthy male subjects, volunteers in IBP single-dose two-way cross-over bioequivalence studies were genotyped for CYP2C9*2, CYP2C9*3 and AKR1D1*36 polymorphisms. The correlation between CYP2C9 and AKR1D1 genetic profile and the PK parameters for S-(+) and R-(-)-IBP was evaluated. Remarkable changes in the PK values pointing to reduced CYP2C9 enzyme activity were detected only in the CYP2C9*2 allelic variant carriers. Statistically significant association between the AKR1D1*36 allele and the increased IBP metabolism (low AUC0-t and 0-∞, high Cltot and short tmax values for both enantiomers) was observed in subjects carrying the CYP2C9 *1/*3 or CYP2C9*1/*1 genotype. The clinical value of concomitant CYP2C9 and AKR1D1 genotyping has to be further verified. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Effects of single nucleotide polymorphisms and haplotypes of the SLCO1B1 gene on the pharmacokinetic profile of atorvastatin in healthy Macedonian volunteers(Govi-Verlag (Germany)/Ingenta Connect, 2015-07); ; ; Eftimov, AOATP1B1 is an influx transporter known to mediate the uptake of various endogenous compounds and xenobiotics. Several sequence variations have been discovered in the SLCO1B1 gene encoding OATP1B1. The aim of this study was to investigate the effects of SLCO1B1 polymorphisms on the pharmacokinetics of atorvastatin in healthy volunteers of Macedonian origin. Twenty three participants, genotyped for SLCO1B1 c.388A > G, c.521T > C, c.571T > C, c.597C > T, c.1086C > T, c.1463G > C and c.*439T > G polymorphisms using TaqMan allelic discrimination assay, ingested a single 80 mg dose of atorvastatin. The plasma concentrations of atorvastatin were measured for 48 h using Tandem Liquid Chromatography-Mass Spectrometry, LC-MS-MS, and the peak plasma concentration (C(max)), time to peak plasma concentration (T(max)), elimination half-life (t1/2), constant rate of elimination (k(el)), mean residence time (MRT, expo), volume of distribution (Vd/kg), clearance (CL/kg), area under curve AUC(0.48h) and AUC(0-∞), were determined. Our data confirmed that the SLCO1B1 gene is highly polymorphic, with a frequency of the c.521T > C single-nucleotide polymorphism (SNP) being the lowest (app. 15%) and of all other SNPs alleles above 40%. Exceptions were c.1463G > C and c.1086C > T SNPs for which variant alleles were not identified. The strongest correlation was observed between the c.521T > C and c.571T > C SNPs pair. The haplotype analysis revealed 10 different haplotypes, with *1J/*1K/*1L being the dominant, with a frequency of app. 40%. The haplotype *15/*16/*17, containing both variant alleles of the functionally most distinguished SNPs, c.388A > G and c.521T > C, occurred with a frequency of 13%. However, *15/*16/*17 homozygotes were not identified in the study group. In this study, no significant differences in the k(el), t1/2, C(max), T(max), AUC(0-48h), AUC(0-∞), MRT expo, Vd and CL between the carriers of different c.388A > G, c.597C > T and c.*439T > G genotypes were observed. Subject with a variant allele C in the c.521T > C SNP, c.521CC genotype, had markedly higher values for C(max) and AUC(0.48h), 140% and 67%, respectively, in comparison with the carriers of the c.521TT genotype. Also, the carriers of the variant allele C at c.571T > C SNP, c.571 CC genotype, had 55% and 43% lower mean C(max) and AUC(0-48h) in comparison with the carrier of c.571TT. These differences lacked statistical significance due to the size of the sample. In addition, no significant differences in the pharmacokinetic parameters of atorvastatin between the *15/*16/*17 heterozygotes and *15/*16/*17 non-carriers were observed. In conclusion, this extensive analysis of the effect of SLCO1B1 polymorphisms on the pharmacokinetic profile of atorvastatin showed that c.521T > C and c.571T > C SNPs may affect the inter-individual response to atorvastatin. Additional studies, with a large sample size, are needed to confirm this finding. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Botilinum toxin in the treatment of strabismus(Macedonian Pharmaceutical Association, 2022); - Some of the metrics are blocked by yourconsent settings
Item type:Publication, DIFFERENTIAL EFFECTS OF PEROXISOME PROLIFERATORACTIVATOR RECEPTOR (PPAR) ALPHA AND GAMMA AGONISTS ON BODY WEIGHT AND ADIPOSE DEPOTS IN FRUCTOSE FED WISTAR RATS(Macedonian Association of Anatomists, 2018); ; ; ; The aim of this study was to investigate the effect of fenofibrate (PPARalpha agonist) and rosiglitazone (PPAR-gamma agonist) on body weight and adipose depots in an experimental model of the metabolic syndrome. Metabolic syndrome was induced in 48 male Wistar rats by adding a fructose in drinking water (10% solution) for 12 weeks. During the last 4 weeks, 16 rats were treated with fenofibrate (100 mg/kg/day), 16 rats were treated with rosiglitazone (5 mg/kg/day) by intragastric tube, while the remaining 16 did not receive any medication (fructose group). Another control group of 16 rats consumed standard rat chow and water for 12 weeks. Chronic fructose administration for 12 weeks significantly increased the body weight (p<0.05), as well as the weight of the measured fat pads: perirenal (p<0.001) and epididymal (p<0.001) as representatives of the visceral adipose depots and the inguinal pads (p<0.05) as a representative of the subcutaneous adipose depots compared to the control group. This was accompanied with a decrease of the subcutaneous/visceral fat ratio. Treatment with fenofibrate over the final 4 weeks significantly decreased the body weight (p<0.001) and the weight of the epididymal, perirenal and inguinal fat pads (p<0.001 for all parameters), without changes of the subcutaneous/visceral fat ratio. On the other hand, rosiglitazone promoted weight gain. Treatment with this PPAR-gamma agonist significantly decreased the weight of the epididymal (p<0.01) and perirenal (p<0.05) pads, but increased the weight of the inguinal fat pads (p<0.001) compared to the fructose group, which led to an increase of the subcutaneous/visceral fat ratio. This study indicates that treatment with the PPAR-alpha agonist fenofibrate decreases body weight and reduces the fat depots, whereas PPAR-gamma agonist promotes weight gain and a body fat redistribution from visceral towards subcutaneous depots in an animal nutritive model of the metabolic syndrome