Interindividual variability in drug metabolism is an important cause of adverse drug reactions and variability in drug efficiency. Polymorphisms of cytochrome P450 (CYPs) genes have a significant effect on drug metabolism and toxicity. This review brings an update about how genetic polymorphisms of CYP2C8 and CYP2C9 enzymes affect the disposition and clinical outcomes of ibuprofen and diclofenac, two of the most common pain relievers. The most common side effects associated with the influence of CYP2C8*3 and CYP2C9*2*3 variants on ibuprofen and diclofenac pharmacokinetics are hepatotoxicity and gastrointestinal bleeding. CYP genotyping may therefore identify patients at increased risk of these adverse reactions, and these patients could have their doses adjusted or start receiving another NSAID that does not share the same metabolic pathways with ibuprofen or diclofenac. However, before genotyping is introduced into regular clinical practice, more research is needed to evaluate the effectiveness of this strategy in improving treatment with ibuprofen and diclofenac.

Cytochrome P450 genetic polymorphisms are responsible for individual variations in drug metabolism and drug-drug interactions. They are very important for pharmacogenetics, and their frequency varies across different populations. There is a big gap in the knowledge about the CYP gene family polymorphisms in the population of Kosovo, and the aim of our study was to fill that gap by determining the frequency of the most important variant alleles of CYP2C9, CYP2C19, and CYP3A5 in 234 nonrelated Kosovars. The allele frequencies of CYP2C9*2 and 2C9*3 were 17.52 %, and 10.89 %, respectively. Sixteen participants (6.81 %) were CYP2C9 poor metabolisers. The CYP2C19*2 and *17 variant frequencies were 13.03 % and 19.01 %, respectively. There were 2.13 % CYP2C19 poor and 4.27 % ultra-rapid metabolisers (homozygous carriers of the *17 allele). With regard to CYP3A5, the frequency of the *3 variant allele was 98.29 % (non-expressors), while the remaining participants (1.70 %) were expressors of CYP3A5. These findings are comparable with other European ethnicities, specifically those of Southeast Europe. KEY WORDS: cytochrome P450 enzyme system; drug metabolism; pharmacogeneticsIndividual variability in response to the most common drugs presents one of the major challenges to pharmacotherapy today. This variability depends on a variety of factors (drug interactions, hepatorenal disorders, sex, age, and lifestyle), but the most challenging are the genetic polymorphisms that have a direct and important impact on drug-detoxifying enzymes, drug targets, and drug transporters (1-3). Phase I enzymes metabolise nearly 59 % of the drugs reported for adverse drug reactions (ADR), and cytochromes P450 (CYP450 or CYP) make 75-86 % of these phase I enzymes (2, 4). Their genetic variants are responsible for unintended drug metabolism and interactions (5) that can lead to toxicity or failed pharmacotherapy (6). This has been recognised by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA), as both push policies requiring that pharmacogenetic information is provided for drug development and postmarketing surveillance (7,8).The most important genetic variants of CYP in clinical practice include those of CYP2C9, CYP2C19, and CYP3A5. Their frequencies vary across populations, and mapping them, so to speak, can be very useful in designing specific pharmacotherapy. To the best of our knowledge no such mapping has been done for the population of Kosovo, a southeast European country of over 1.7 million people, 93 % of whom are ethnic Albanians. The aim of our study was to address this gap and determine the frequency of the pharmacologically most important variant alleles of CYP2C9, CYP2C19, and CYP3A5 in Kosovo population, hoping that our findings could help to optimise pharmacotherapy in the country. PARTICIPANTS AND METHODSThis study included a mixed population of 234 randomly selected Caucasians (116 women and 118 men) with no blood relation from all parts of Kosovo. Their age ranged between 18 and 65 years (median: 3...

ObjectivesThere are no reliable data on antibiotic use in Kosovo hospitals. The aim of this survey was to monitor volumes and patterns of antibiotic use in hospitalised patients in order to identify targets for quality improvement.MethodsData on antimicrobial use were collected from seven hospitals in Kosovo during 2013 using the standardised point prevalence survey (PPS) methodology as developed by the ESAC (European Surveillance of Antimicrobial Consumption) and ARPEC (Antibiotic Resistance and Prescribing in European Children). The survey included all inpatients receiving an antimicrobial agent on the day of the PPS.ResultsOverall, 1667 patients were included in the study: adults 1345 (81%) and children 322 (19%). Of the hospital inpatients, 579/1345 (43%) adults and 188/322 (58%) children received at least one antibiotic during a hospital stay. The top three antibacterial subgroups (ATC level 3) were β-lactam antibiotics, cephalosporins and aminoglycosides. In all hospital centres, the most commonly prescribed antibiotic was ceftriaxone (39% for adult and 36% for children). Antibiotics were administered mainly parenterally in 74% of adults and 94% of children. Empirical prescribing was higher in adults 498/579 (86%) and children 181/188 (96%), compared with targeted treatment based on susceptibility testing—81 (14%) and 8 (4%), respectively.ConclusionsAntibiotic use in Kosovo’s hospitals is very high. Gathered data will be an important tool to identify targets for quality improvement and will support preparation of guidelines and protocols for the prudent use of antibiotics.

BACKGROUND:Antibiotics are among the most commonly prescribed drugs in paediatrics. In most cases, antibiotics are started on an empirical basis, without proof of a bacterial infection, either before the start of therapy or afterwards.AIM:The main objective of this study was to analyse the consumption of antibiotics in hospitalised paediatric patients.MATERIAL AND METHODS:This retrospective study investigated the consumption of antimicrobials in defined daily doses (DDDs according to the Anatomical Therapeutical Chemical/DDD index) in Pulmonology, Gastroenterology and Nephrology Departments at Pediatric Clinic of the tertiary hospital. The data on the consumption of antimicrobials were collected for five years by using properly designed form. The consumption was related to days of hospital care.RESULTS:The most utilised antibiotics group in all three departments Pulmonology, Gastroenterology and Nephrology Departments were penicillins. Cephalosporins were mostly used in Pulmonology department. Metronidazole and Chloramphenicol were used in minimal quantities in all three departments.CONCLUSION:This study demonstrates that surveillance programs on antibiotic resistance should be established and accompanied by analyses of drug utilisation data which can aid in the creation of valid cross-national studies on antibiotic usage and resistance, to motivate improvements in prescribing and guideline-directed antibiotic prescribing.