Katalog istraživačkog i inovativnog potencijala
Univerziteta u Novom Sadu

• Istraživanje metabolizma lekova u in vivo i in vitro uslovima
• Razvoj analitičkih metoda za farmakokinetske studije
• Uticaj farmaceutske formulacije na farmakokinetiku lekova
• Novi lekovi antidijabetika
• Novi derivati žučne kiseline
• Prolaz lekova kroz biološke membrane

Rezultati istraživanja našeg tima pokazali su da žučne kiseline same ispoljavaju značajan hipoglikemijski efekat i na taj način mogu da potenciraju efekat drugih hipoglikemika. Hipoglikemijski efekat kod dijabetičnih životinja utvrđen je i nakon primene probiotikakoji ovaj efekat ostvaruju insulin-nezavisnim mehanizmima.Najizraženiji hipoglikemijski efekat kod dijabetičnih životinja uočen je kod kombinovane primene žučnih kiselina sa gliklazidom i probioticima sugerišući na značajne interakcije između ovih supstanci čiji mehanizmi na molekularnom nivou tek treba da se ispitaju. Utvrđeno je takođe da polusintetski derivat žučne kiseline, 12-monoketoholna kiselina (MKC) ima potencijal da modifikuje biofizička svojstva ćelijske membrane i da utiče na funkciju i aktivnost transportnih proteina vezanih za membranu, menjajući transport lekova kroz biološke membrane što kao posledicu može da ima izmenjene farmakokinetske karakteristike leka. Tako je pokazano da MKC povećava isporuku lekova o centralnog nervnog sistema, povećava apsorpciju tramadola i transport do mozga i na taj način utiče na povećanjenjegovog analgetskog efekata. Slično, pokazano je da deoksiholna kiselina dovodi do povećanog prenosa glikazida do CNS-a. Najverovatniji mehanizam prolaska je modifikacija i otvaranjetesnih veza u KMB ili inkorporiranje deoksiholne kiseline u ćelijsku membranu čime jeolakšan prenos gliklazida. Pored toga, rezultati tima pokazali su značajne izmene farmakokinetičkih parametara MKC i gliklazida nakon peroralne primene nakon tretmana probioticima, ukazujući na značaj probiotika i crevne mikroflore u izmeni farmakokinetskih i farmakodinamskih osobina farmakološki aktivnih supstanci.

Radovi publikovani u časopisima sa SCI liste u toku 2017. godine:

1. Mikov M, Ðanić (Stojančević) M, Pavlović N, Stanimirov B, Goločorbin-Kon S, Stankov K, Al-Salami H. The Role of Drug Metabolites in the Inhibition of Cytochrome P450 Enzymes. Eur J Drug Metab Pharmacokinet. 2017: DOI 10.1007/s13318-017-0417-y

2. Ilić V, Vukmirović S, Stilinović N, Čapo I, Arsenović M, Milijašević B. Insight into anti-diabetic effect of low dose of stevioside. Biomedicine & Pharmacotherapy 2017;90:216-21.

3. Vukmirovic S, Kusturica M, Milijasevic B, Trifunovic J, Tomas A, Mikov M. Fermentation Potentiates Antimotility Properties of Chamomile Ligulate Flower Extracts. Indian Journal of Pharmaceutical Sciences 2017;78(5):691-4.

4. Zaimović-Šahman M, Vukmirović S, Tomić N, Stilinović N, Horvat O, Tomić Z. Relationship between outpatient antibiotic use and the prevalence of bacterial infections in Montenegro. Vojnosanitetski pregled 2017;74(1):46-50.

5. Rašković A, Gigov S, Čapo I, Kusturica MP, Milijašević B, Kojić-Damjanov S, Martić N. Antioxidative and Protective Actions of Apigenin in a Paracetamol-Induced Hepatotoxicity Rat Model. European Journal of Drug Metabolism and Pharmacokinetics 2017;2:1-8.

6. Tomas A, Kusturica MP, Tomić Z, Horvat O, Koprivica DD, Bukumirić D, Sabo A. Self-medication with antibiotics in Serbian households: a case for action?. International Journal of Clinical Pharmacy 2017. 8:1-7.

7. Paut Kusturica M, Tomas A, Sabo A. Disposal of Unused Drugs: Knowledge and Behavior Among People Around the World. Rev Environ Contam Toxicol. 2017;240:71-104.

Radovi publikovani u časopisima sa SCI liste u toku 2016. godine:

1. Đanić (Stojančević) M, Pavlović N, Stanimirov B, Vukmirović S, Nikolić K, Agbaba D, Mikov M. The influence of bile salts on the distribution of simvastatin in octanol/buffer system. Drug Dev Ind Pharm. 2016;42(4):661-7.

2. Đanić (Stojančević) M, Pavlović N, Stanimirov B, Stojančević T, Goločorbin-Kon S, Bojić G, Mikov M. Docking-based preliminary study on the interactions of bile acids with drugs at the transporter level in intestinal bacteria. Eur Rev Med Pharmaco. 2016;20(3):553-60.

3. Samojlik I, Petković S, Stilinović N, Vukmirović S, Mijatović V, Božin B. Pharmacokinetic Herb-Drug Interaction between Essential Oil of Aniseed (Pimpinella anisum L., Apiaceae) and Acetaminophen and Caffeine: A Potential Risk for Clinical Practice. Phytotherapy Research 2016. 30(2):253-9.

4. Paut Kusturica M, Tomas A, Tomic Z, Bukumiric D, Corac A, Horvat O, Sabo A. Analysis of expired medications in Serbian households. Zdr Varst. 2016;55(3):195-201.

5. Tomić Z, Tomas A, Vukmirović S, Mikov M, Horvat O, Tomić N, Sabo A. Do We Bury Antibacterials When Launching? Cefaclor Example. Journal of pharmaceutical sciences. 2016;105(3):1295-300.

6. Tomas A, Tomić Z, Milijašević B, Ban M, Horvat O, Vukmirović S, Sabo A. Patterns of prescription antihypertensive drug utilization in Novi Sad and adherence to treatment guidelines. Vojnosanitet pregled. 2016 73(6): 531–537.

Radovi publikovani u časopisima sa SCI liste u toku 2015. godine:

1. Mooranian A, Negrulj R, Mathavan S, Martinez J, Sciarretta J, Chen-Tan N, Mukkur TK, Mikov M, Lalic-Popovic M, Đanić (Stojančević) M, Golocorbin-Kon S, Al-Salami H. An advanced microencapsulated system: a platform for optimized oral delivery of antidiabetic drug-bile acid formulations. Pharm Dev Technol. 2015;20(6):702-9.

2. Čapo I, Hinić N, Lalošević D, Vučković N, Stilinović N, Marković J, Sekulić S.Vitamin C Depletion in Prenatal Guinea Pigs as a Model of Lissencephaly Type II. Veterinary Pathology. 2015. 52(6):1263-1271

3. Paut-Kusturica M, Tomić Z, Bukumirić N, Ninković Lj, Tomas A, Stilinović N, Sabo A. Home pharmacies in Serbia: an insight into self-medication practice. International Journal of Clinical Pharmacy 2015. 37(2):373-378

4. Sabo A, Tomas A, Tomić N, Mikov M, Horvat O, Popović R, Tomić Z. Pharmacokinetic/pharmacodynamic based dosing of ciprofloxacin in complicated urinary tract infections. Bangladesh Journal Of Pharmacology. 2015; 10(3): 621-626.

5. Kusturica MP, Tomic Z, Bukumiric Z, Horvat O, Pavlovic N, Mikov M, Sabo A. Antibiotics in Serbian Households: A Source of Potential Health and Environmental Threats?. Central European Journal of Public Health. 2015;23(2):114.

Radovi publikovani u časopisima sa SCI liste u toku 2014. godine:

1. Đanić (Stojančević) M, Bojić G, Salami HA, Mikov M. The Influence of Intestinal Tract and Probiotics on the Fate of Orally Administered Drugs. Curr Issues Mol Biol. 2014;16(2):55-68.

2. Mooranian A, Negrulj R, Mathavan S, Martinez J, Sciarretta J, Chen-Tan N, Mukkur T, Mikov M, Lalic-Popovic M, Đanić (Stojančević) M, Golocorbin-Kon S, Al-Salami H. Stability and Release Kinetics of an Advanced Gliclazide-Cholic Acid Formulation: The Use of Artificial-Cell Microencapsulation in Slow Release Targeted Oral Delivery of Antidiabetics. J Pharm Innov. 2014;9:150-7.

3. Milijašević B, Stefanović D, Lalić-Popović M, Tomić Z, Kolarović J, Lalošević D, Mikov M. Acute toxic effects of single dose dacarbazine: hematological and histological changes in an animal model. Biotech Histochem. 2014 Nov;89(8):583-90. doi: 10.3109/10520295.2014.918653.

4. Vasović V, Rasković A, Mikov M, Mikov I, Milijasević B, Vukmirović S, Budakov Z. Effect of aqueous solution of stevioside on pharmacological properties of some cardioactive drugs.Vojnosanit Pregl. 2014 Jul;71(7):667-72.

5.Vasović V, Vukmirović S, Mikov M, Mikov I, Budakov Z, Stilinović N, Milijasević B. Influence of bile acid derivates on morphine analgesic effect in mice. Vojnosanit Pregl. 2014 Aug;71(8):767-71.

6. Mijatović V, Samojlik I, Ajduković N, Đurendić-Brenesel M, Petković S. Methadone-related deaths – epidemiological, pathohistological, and toxicological traits in 10-year retrospective study in Vojvodina, Serbia. J Forensic Sci. 2014 Sep;59(5):1280-5. doi: 10.1111/1556-4029.12425.

7. Stilinović N, Skrbić B, Zivančev J, Mrmoš N, Pavlović N, Vukmirović S. The level of elements and antioxidant activity of commercial dietary supplement formulations based on edible mushrooms. Food Funct. 2014 Oct 8. doi: 10.1039/c4fo00703d .

Radovi publikovani u časopisima sa SCI liste u toku 2013. godine:

1. Lalić-Popović M, Vasović V, Milijašević B, Goločorbin-Kon S, Al-Salami H, Mikov M. Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat. J Diabetes Res. 2013;2013:598603. doi: 10.1155/2013/598603.

2. Stepanov V, Stankov K, Mikov M. The bile acid membrane receptor TGR5: a novel pharmacological target in metabolic, inflammatory and neoplastic disorders. J Recept Signal Transduct Res. 2013 Aug;33(4):213-23. doi: 10.3109/10799893.2013.802805. 3. Odalovic M, Vezmar Kovacevic S, Nordeng H, Ilic K, Sabo A, Tasic L. Predictors of the use of medications before and during pregnancy. Int J Clin Pharm. 2013 Jun;35(3):408-16. doi: 10.1007/s11096-013-9750-7. 4. Sabo A, Horvat O, Stilinovic N, Berenji J, Vukmirovic S. Industrial hemp decreases intestinal motility stronger than indian hemp in mice. Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):486-90.

5. Lalic-Popovic M, Paunkovic J, Grujic Z, Golocorbin-Kon S, Al-Salami H, Mikov M. Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women. BMC Pregnancy Childbirth. 2013 Oct 17;13(1):188.

6. Mihajlović J, Pechlivanoglou P, Sabo A, Tomić Z, Postma MJ. Cost-effectiveness of everolimus for second-line treatment of metastatic renal cell carcinoma in Serbia. Clin Ther. 2013 Dec;35(12):1909-22. doi: 10.1016/j.clinthera.2013.10.004.

7. Đanić (Stojančević) M, Pavlović N, Goločorbin-Kon S, Mikov M. Application of bile acids in drug formulation and delivery. Frontiers in Life Science (HFSP Journal) 2013;7(3-4):112-122 DOI:10.1080/21553769.2013.879925

8. Samojlik I, Mijatović V, Gavarić N, Krstin S, Božin B. Consumers’ attitude towards the use and safety of herbal medicines and herbal dietary supplements in Serbia. Int J Clin Pharm. 2013 Oct;35(5):835-40. doi: 10.1007/s11096-013-9819-3.

9. Andrejić BM, Mijatović VM, Samojlik IN, Horvat OJ, Ćalasan JD, Đolai MA. The influence of chronic intake of saccharin on rat hepatic and pancreatic function and morphology: gender differences. Bosn J Basic Med Sci. 2013 May;13(2):94-9.

10. Mijatović V, Dickov A, Petković S, Popov T, Samojlik I. Safety assessment of low doses of methadone in combination with benzodiazepines in real occasions during methadone maintenance treatment. Heroin Addict Relat Clin Probl 2013;15(3): 29-34. .

Radovi publikovani u časopisima sa SCI liste u toku 2012. godine:

1. Stanimirov B, Stankov K, Mikov M. Pleiotropic functions of bile acids mediated by the farnesoid X receptor. Acta Gastroenterol Belg. 2012 Dec;75(4):389-98.

2. Velickovic-Radovanovic R, Mikov M, Catic-Djordjevic A, Stefanovic N, Stojanovic M, Jokanovic M, Cvetkovic T. Tacrolimus as a part of immunosuppressive treatment in kidney transplantation patients: sex differences.Gend Med. 2012 Dec;9(6):471-80. doi: 10.1016/j.genm.2012.10.003.

3. Pavlović N, Stankov K, Mikov M. Probiotics–interactions with bile acids and impact on cholesterol metabolism.Appl Biochem Biotechnol. 2012 Dec;168(7):1880-95. doi: 10.1007/s12010-012-9904-4.

4. Đanić (Stojančević) M, Stankov K, Mikov M. The impact of farnesoid X receptor activation on intestinal permeability in inflammatory bowel disease.Can J Gastroenterol. 2012 Sep;26(9):631-7.

5. Stankov K, Draskovic D, Mikov M. Ethical and legal aspects of oncogenomics. J BUON. 2012 Apr-Jun;17(2):383-8.

6. Mikov I, Stankov K, Vasovic V, Mikov A, Golocorbin-Kon S, Mikov M. Effect of simultaneous exposure to benzene and ethanol on urinary thioether excretion. Int J Occup Saf Ergon. 2012;18(1):107-11

7. Sabo A, Horvat O, Stilinovic N, Berenji J, Vukmirovic S. Industrial hemp decreases intestinal motility stronger than indian hemp in mice. Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):486-90.

8. Kusturica MP, Sabo A, Tomic Z, Horvat O, Solak Z. Storage and disposal of unused medications: knowledge, behavior, and attitudes among Serbian people. Int J Clin Pharm. 2012 Aug;34(4):604-10. doi: 10.1007/s11096-012-9652-0.

9. Pavlović N, Stanimirov B, Stojančević M, Paut-Kusturica M, Stoimenova A, Goločorbin-Kon S, Mikov M. An insight on differences in availability and reimbursement of orphan medicines among Serbia, Bulgaria and Sweden.Biotechnol & Biotechnol Eq. 2012; 26(5):3236-41.

10. Odalovic M, Vezmar Kovacevic S, Ilic K, Sabo A, Tasic L. Drug use before and during pregnancy in Serbia. Int J Clin Pharm. 2012 Oct;34(5):719-27. doi: 10.1007/s11096-012-9665-8.

11. Horvat O, Mijatović V, Čalasan J, Sabo A. Outpatient utilization of non-steroidal anti-inflammatory drugs in three largest municipalities in South Backa district. Srp Arh Celok Lek. 2012 May-Jun;140(5-6):339-43. Serbian.

12. Al-Salami H, Butt G, Tucker I, Golocorbin-Kon S, Mikov M. Probiotics decreased the bioavailability of the bile acid analog, monoketocholic acid, when coadministered with gliclazide, in healthy but not diabetic rats. Eur J Drug Metab Pharmacokinet. 2012 Jun;37(2):99-108. doi: 10.1007/s13318-011-0060-y.

13. Vapa I, Torres VM, Djordjevic A, Vasovic V, Srdjenovic B, Simic VD, Popović JK. Effect of fullerenol C(60)(OH) (24) on lipid peroxidation of kidneys, testes and lungs in rats treated with doxorubicine. Eur J Drug Metab Pharmacokinet. 2012 Dec;37(4):301-7. doi: 10.1007/s13318-012-0092-y.

14. Erić M, Leppée M, Sabo A, Culig J. Beta-lactam antibiotics during pregnancy: a cross-sectional comparative study Zagreb-Novi Sad. Eur Rev Med Pharmacol Sci. 2012 Jan;16(1):103-10.

15. Samojlik I, Mijatović V, Petković S, Skrbić B, Božin B. The influence of essential oil of aniseed (Pimpinella anisum, L.) on drug effects on the central nervous system. Fitoterapia. 2012 Dec;83(8):1466-73. doi: 10.1016/j.fitote.2012.08.012. .

Radovi publikovani u časopisima sa SCI liste u toku 2011. godine:

1. Sabo A, Tomić Z, Stilinović N, Milijašević B, Mikov M, Vukmirović S, Horvat O. Consumption of serum lipid-reducing drugs in Serbia compared with Scandinavian countries: a population-based study, 2004-2008. Pharmacoepidemiol Drug Saf. 2011 Jan;20(1):45-9. doi: 10.1002/pds.2045.

2. Perisić Z, Perisić N, Golocorbin Kon S, Vesović D, Jovanović AM, Mikov M. The influence of probiotics on the cervical malignancy diagnostics quality.Vojnosanit Pregl. 2011 Nov;68(11):956-60.

3. Cekić V, Vasović V, Jakovljević V, Lalošević D, Čapo I, Mikov M, Sabo A. Effect of chromium enriched fermentation product of barley and brewer’s yeast and its combination with rosiglitazone on experimentally induced hyperglycaemia in mice. Srp Arh Celok Lek. 2011 Sep-Oct;139(9-10):610-8. Serbian.

4. Rašković A, Stilinović N, Kolarović J, Vasović V, Vukmirović S, Mikov M. The protective effects of silymarin against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats. Molecules. 2011 Oct 12;16(10):8601-13. doi: 10.3390/molecules16108601.

5. Al-Salami H, Butt G, Tucker I, Golocorbin-Kon S, Mikov M. Probiotics decreased the bioavailability of the bile acid analog, monoketocholic acid, when coadministered with gliclazide, in healthy but not diabetic rats.Eur J Drug Metab Pharmacokinet. 2012 Jun;37(2):99-108. doi: 10.1007/s13318-011-0060-y.

6. Golocorbin Kon S, Mikov M. Counterfeit drugs as a gobal threat to health.Med Pregl. 2011 May-Jun;64(5-6):285-90.

7. Velicković-Radovanović R, Mikov M, Paunović G, Djordjević V, Stojanović M, Cvetković T, Djordjević AC. Gender differences in pharmacokinetics of tacrolimus and their clinical significance in kidney transplant recipients. Gend Med. 2011 Feb;8(1):23-31. doi: 10.1016/j.genm.2011.01.003.

8. Calasan J, Mijatović V, Horvat O, Varga J, Sabo A, Stilinović N. The outpatient utilization of non-steroidal anti-inflammatory drugs in South Bačka District, Serbia.Int J Clin Pharm. 2011 Apr;33(2):246-51. doi: 10.1007/s11096-011-9487-0.

9. Lalic M, Pilipovic A, Golocorbin-Kon S, Gebauer-Bukurov K, Bozic K, Mikov M, Cvejic J. Comparison of dissolution profiles and serum concentrations of two lamotrigine tablet formulations.Drugs R D. 2011;11(1):53-60. doi: 10.2165/11588260-000000000-00000.

10. Cekic V, Vasovic V, Jakovljevic V, Mikov M, Sabo A. Hypoglycaemic action of stevioside and а barley and brewer’s yeast based preparation in the experimental model on mice. Bosn J Basic Med Sci. 2011 Feb;11(1):11-6.

11. Duborija-Kovacevic N, Jakovljevic V, Sabo A, Tomic Z, Pajovic B, Perovic D. Tolerability and toxicity of lipidosterolic extract of American dwarf palm Serenoa repens in Wistar rats: well-known extract, new insight. Eur Rev Med Pharmacol Sci. 2011 Nov;15(11):1311-7.

12. Mijatović V, Calasan J, Horvat O, Sabo A, Tomić Z, Radulović V. Consumption of non-steroidal anti-inflammatory drugs in Serbia: a comparison with Croatia and Denmark during 2005-2008. Eur J Clin Pharmacol. 2011 Feb;67(2):203-7. doi: 10.1007/s00228-010-0951-x. .