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Photodegradation of 3 commonly used nonsteroidal anti-inflammatory drugs, ketoprofen, carprofen, and diclofenac acid, was conducted under ultraviolet (UV) irradiation. The kinetic results showed that the 3 pharmaceuticals obeyed the first-order reaction with decreasing rate constants of 1.54 × 10 -4 , 5.91 × 10 -5 , and 7.78 × 10 -6  s -1 for carprofen, ketoprofen, and diclofenac acid, respectively. Moreover, the main transformation products were identified by ion-pair liquid-liquid extraction combined with injection port derivatization-gas chromatography-mass spectrometry and high-performance liquid chromatography-quadrupole-time of flight mass spectrometric analysis. There were 8, 3, and 6 transformation products identified for ketoprofen, carprofen, and diclofenac acid, respectively. Decarboxylation, dechlorination, oxidation, demethylation, esterification, and cyclization were proposed to be associated with the transformation of the 3 pharmaceuticals. Toxicity prediction of the transformation products was conducted on the EPI Suite software based on ECOSAR model, and the results indicate that some of the transformation products were more toxic than the parent compounds. The present study provides the foundation to understand the transformation behavior of the studied pharmaceuticals under UV irradiation. Environ Toxicol Chem 2017;36:3232-3239. © 2017 SETAC., (© 2017 SETAC.)

The occurrence of pharmaceutical compounds in wastewater treatment plants and surface waters has been detected worldwide, constituting a potential risk for aquatic ecosystems. Adult zebrafish, of both sexes, were exposed to three common pharmaceutical compounds (atenolol, ketoprofen and diclofenac) and their UV photolysis by-products over seven days. The results show that diclofenac was removed to concentrations

A study was undertaken to assess the hepatotoxic and nephrotoxic potential of ketoprofen in comparison with diclofenac upon short-term intramuscular (i.m.) administration in broiler chickens. Eighteen broiler chickens were randomly divided into 3 groups of 6 birds each. Group I served as the control and received normal saline (0.1 mL, i.m.), group II was the positive control and received diclofenac sodium (2.5 mg/kg, i.m.), and group III received ketoprofen (3 mg/kg, i.m.) daily at 24-h intervals for 5 consecutive days. Diclofenac sodium-treated birds showed severe clinical signs of toxicity with high mortality, a significant increase (P < 0.01) in serum concentrations of creatinine, uric acid, alanine aminotransferase, and aspartate aminotransferase, and these changes correlated well with gross and microscopic examination findings of kidney and liver. In contrast, ketoprofen-treated birds did not show any adverse clinical signs and no significant increase in concentration of creatinine, uric acid, alanine aminotransferase, and aspartate aminotransferase when compared with birds in group I. Gross and microscopic examination of kidney and liver showed normal organ architecture. Thus, based on the present findings, it was concluded that ketoprofen at the dose of 3 mg/kg administered intramuscularly daily for 5 d was nontoxic to broiler chickens.

In the last years there appeared many articles about the adverse influence of non-steroidal anti-inflammatory drugs on the liver and heart. This study is concerned with the influence of the duration of treatment with diclofenac and ketoprofen on the macroscopic and microscopic changes in the liver, lungs, heart, and kidneys in rats. Experiments were carried out on mature Wistar strain rats. Animals of test groups received diclofenac and ketoprofen in a dose of 8 mg/kg/day (equivalent to the therapeutic dose for man) during 7 per os (p.o.) or 28 days intraperitoneally (i.p.), whereas controls received physiological solution p.o. A high morbidity was observed in the animals receiving diclofenac p.o. and somewhat lower in those treated with ketoprofen. On the other hand, the rats got through the 28-day i.p. treatment with both drugs mainly without significant complications. Macroscopic examinations revealed some changes in treated rats: distension of the stomach, ascites, fibrin deposits on the internal organs, lung effusion and the changes in color and structure of the liver. These changes were more frequent in the group of rats receiving diclofenac for the 7 days compared with those that received ketoprofen for the same time. It may be thought that the high mortality and macroscopic changes in the internal organs of experimental animals are a consequence of the microscopic changes in the liver and its lowered function.

Polyoxyethylene esters of ketoprofen (1a-e), naproxen (2a-e) and diclofenac (3a-e) were tested in vitro to determine their stability in pH 7.4 phosphate buffer and in simulated gastric fluid (pH 2.0 buffer) and their susceptibility in undergoing enzymatic cleavage in human plasma. Furthermore their in vivo antiinflammatory and analgesic activity and GI toxicity were evaluated in rodents. All the prodrugs showed a good stability both in pH 7.4 phosphate buffer and in pH 2.0 buffer. They were readily hydrolyzed by human plasma and, for each group of prodrugs, no significant difference in hydrolysis rate was observed as the length of the oligoethylene chain increased. Esters 1a-e, 2a-e and 3a-e showed an anti-inflammatory activity (expressed as inhibition percent of carrageenan-induced edema in the rat) similar to that of their respective parent drug although at higher doses. The results obtained in the writhing test in mice demonstrated that all the prodrugs tested exhibited, following acute administration, a good analgesic effect. Furthermore these esters were significantly less irritating to the gastric mucosa, although administered at doses higher than the respective parent drug.

The aim of this experimental study was to investigate the effect of diclofenac sodium and ketoprofen, two non-steroidal anti-inflammatory drugs (NSAIDs) with different excretion pathways, and the role of other enteric factors during simultaneous administration of these drugs on the development of mucosal lesions of the small intestine in canines. Twenty-five animals were divided into three groups. Group I included 10 canines, 5 with diclofenac sodium (group Ia) and 5 with ketoprofen administration (group Ib). Group II included 5 animals in which a segment of ileum was surgically isolated from the rest of the small intestine. Group III included 10 animals in two subgroups of 5; a segment of ileum was surgically isolated in both subgroups; groups IIIa received diclofenac and group IIIb ketoprofen. Histological examination of the specimens taken revealed macroscopic and microscopic mucosal lesions in 5/5 animals in group Ia, whereas none of the 5 animals in group Ib had any lesions. Group II did not reveal any mucosal lesions. Three out of 5 animals (60%) administered diclofenac in group IIIa had intestinal mucosal lesions, but none of the 5 revealed lesions in the isolated loop of ileum. No lesions were observed in the isolated loop or in the rest of the intestinal mucosa in the animals in group IIIb. Our results suggest that NSAIDs produce intestinal mucosal lesions not only when administered per mouth but also after intramuscular administration. Diclofenac, unlike ketoprofen, was responsible for the development of lesions in the intestinal mucosa. The role of drugs and/or their metabolites in the intestine and certain other factors must still be determined.