Diclofenac (2-[(2,6-Dichlorophenyl)amino]benzeneacetic acid) is a non-steroidal anti-infl ammatory

drug. Due to excessive use of diclofenac, this drug has been detected in surface water, ground water and drinking

water. In our study, four fungal strain Trametes trogii, Aspergillus niger, Yarrowia lipolytica and Phanerochaete

chrysosporium were investigated in terms of diclofenac degradation potential. Trametes trogii was found to be

the most effi cient strain with 100% diclofenac degradation rate. Two hydroxylated diclofenac metabolites have

been identifi ed in culture medium. Crude laccase from T. trogii almost completely removed diclofenac with 97%

removal in 48 h. We suggest that the degradation of diclofenac depends on the cytochrome P450 enzyme system

and laccase activity. After 24 h incubation decrease in toxicity of diclofenac was confi rmed by Microtox test.

In environmental matrices there are mixtures of parent drug and its metabolites. The majority of research is focused on the biological activity and toxic effect of diclofenac (DCF), there is little research on the biological activity of DCF metabolites and their mixtures. The study focused on the assessment of the biological impact of DCF, its metabolites 4’-hydroxydiclofenac (4’-OHDCF) and 5-hydroxydiclofenac (5-OHDCF) and their mixtures on E. coli strains. The biological effects of tested chemicals were evaluated using the following: E. coli K-12 cells viability assay, the inhibition of bacteria culture growth, ROS (reactive oxygene species) generation and glutathione (GSH) content estimation. Moreover, we examined the influence of the mixture of DCF with caffeic acid (CA) on E. coli cells viability. Our results showed the strongest impact of the mixtures of DCF with 4’-OHDCF and 5-OHDCF on E. coli SM biosensor strains in comparison to parent chemicals. Similar results were obtained in viability test, where we noticed the highest reduction in E. coli cell viability after bacteria incubation with the mixtures of DCF with 4’-OHDCF and 5-OHDCF. Similarly, these mixtures strongly inhibited the growth of E. coli culture. We also found synergistic effect of caffeic acid in combination with DCF on E. coli cells viability. After bacteria treatment with the mixture of DCF and its metabolites we also noted the strongest amount of ROS generation and GSH depletion in E. coli culture. It suggests that oxidative stress is the most important mechanism underlying the activity of DCF and its metabolites.

The aim of this study was to investigate the cardiotoxic effect of the combination of tilmicosin and diclofenac sodium in sheep. Thirty-two sheep were used and were randomly divided into four equal groups as tilmicosin (T), diclofenac sodium (D), tilmicosin+diclofenac sodium (TD) and control (C) group. Group T received a single dose of tilmicosin, Group D was administered diclofenac sodium once a day for 3 days, and group TD was administered diclofenac and tilmicosin at the same doses as group T and D. Group C received NaCl in a similar way. The blood samples were taken before dosing and at 4th, 8th, 24th and 72nd hour post-dosing for measurement of cardiac markers such as H-FABP, cTn-I, CK-MB. H-FABP level of group TD was found to be significantly (p<0.05) higher than of group C at the 8th, 24th and 72nd hour and group D and T at the 72nd hour. cTn-I and CK-MB levels of group TD were found significantly (p<0.05) higher compared with other groups. In conclusion, the combined use of tilmicosin and diclofenac in sheep causes an increase in cardiac biomarkers and it can be stated that this combination of drugs may cause cardiac damage.

The pharmacokinetics of a diclofenac sodium was investigated in swine. A single intravenous (i.v.) or intramuscular (i.m.) injection of 5% diclofenac sodium (concentration = 2.5 mg · kg-1) was administered to 8 healthy pigs according to a two-period crossover design. The pharmacokinetic parameters were calculated by non-compartmental analysis with DAS2.1.1 software. After a single i.v. administration, the main pharmacokinetic parameters of diclofenac sodium injection in swine were as follows: the elimination half-time (T1/2β) was 1.32±0.34 h; the area under the curve (AUC) was (55.50±5.50 μg · mL-1 h; the mean residence time (MRT) was 1.60±0.28 h; the apparent volume of distribution (Vd) was 0.50±0.05 L · kg-1; and the body clearance (CLB) was 0.26±0.04 L · (h · kg)-1. After the single i.m. administration, the pharmacokinetic parameters were as follows: peak time (Tmax) was 1.19±0.26 h; and peak concentration (Cmax) was 11.61±5.99 μg mL-1. The diclofenac sodium has the following pharmacokinetic characteristics in swine: rapid absorption and elimination; high peak concentration; and bioavailability.

Większość farmaceutyków stosowanych w medycynie nie ulega całkowitemu zmetabolizowaniu w ciele pacjenta i wraz z moczem i kalem trafia do systemu kanalizacyjnego. Ze względu na swe właściwości, nie są one całkowicie usuwane ze ścieków w konwencjonalnych procesach oczyszczania ścieków i wraz ze ściekami oczyszczonymi mogą przedostawać się do odbiorników. Diklofenak jest lekiem często identyfikowanym w wodach powierzchniowych. Prezentowane w niniejszej publikacj i badania dotyczą problemu usuwania diklofenaku ze środowiska wodnego z~ pomocą zaawansowanych procesów utleniania (ang. advanced oxidation processes. AOPs). Badania prowadzono w roztworach wodnych diklofenaku (przygotowanego z wykorzystaniem wody destylowanej) oraz w ściekach po biologicznym procesie oczyszczania. W badaniach zastosowano następujące techniki AOps: utlenianie odczynnikiem Fcntona, utlenianie za pomocą promieniowania UV oraz proces UV/H2O2. Stężenie diklotenaku odpowiadało stężeuiom.jnkich można spodziewać się w moczu pacjenta podczas kuracji tym lekiem (20 mg dm3). Ścieki oczyszczone zawierały dik lofcnak na poziomic 630-790 ngdm3. Badania z wykorzystaniem promieniowania UV prowadzono w Iotorcaktorze wyposażonym w średuiociśnieniową lampę rtęciową (400 W). Utlenianie za pomocą odczynnika Fcntona prowadzono przy różnych stosunkach molowych H2O2,/Fe2. Mineralizacja diklofcnaku (określana jako usunięcie OWO) bezpośrednio zależała od ilości H2O2; odczynniku Fentona stosowanego podczas badań. Diklofenuk ulegał szybkiemu rozkładowi za pomocą promieniowania UV i w procesie UV/H2O2, zarówno w roztworze wodnym tego leku jak i w próbkach ścieków. Wyniki przeprowadzonych badań wsknzują, iż zastosowanie zaawansowanych procesów utleniania w znacznym stopniu zwiększa efektywność usuwania diklofenaku ze środowiska wodnego. W ramach ninicjszych badań obliczone zostały pseudo pierwszorzędowe stale szybkości rozkładu diklotenaku przy zastosowaniu metod fotochemicznych.