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 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.