Le psoriasis est une maladie de peau auto-immune et chronique. Le rhumatisme psoriasique est une de ses principales complications qui est très invalidante pour les patients. Cette pathologie reste encore incurable à ce jour. L'usage des médicaments disponibles actuellement dans le psoriasis est limité par leurs effets secondaires dépendant de la dose et de la durée d'utilisation. Le but de ce travail était de développer des nanovecteurs médicamenteux à base de lipides pour un usage topique, en particulier ciblant l'épiderme viable qui est le site principal de la physiopathologie du psoriasis, mais aussi le derme et au-delà pour atteindre les articulations endommagées. Grâce à une nouvelle technique que nous avons développé et optimisé, le double déplacement de solvants, basée sur une organisation des phospholipides en deux temps, nous avons préparé des vésicules lipidiques encapsulant du diclofénac d'une part et de la ciclosporine A 'autre part. Ensuite, nous avons évalué leur aptitude à traverser la peau et cibler les régions d'intérêt. Après une étude systématique permettant d'optimiser les paramètres de préparation, les vésicules lipidiques encapsulant le diclofénac et la cyclosporine A ont montré une efficacité d'encapsulation (EE%) comprise entre 50% et 90% respectivement, selon la concentration en phospholipides. Après réalisation des études in vitro sur peau de cochon, nous avons observé que la formulation contenant une concentration basse en phospholipides (8,5 mg / mL) permettait d'encapsuler plus de 80% du diclofénac et de cibler le derme et au-delà. La formulation de vésicules lipidiques chargées de cyclosporine A qui encapsule la quantité la plus élevée (environ 80%) était également celle contenant la concentration basse de phospholipides. Contrairement au diclofénac, cette formulation n'était pas la meilleure pour cibler une couche profonde de la peau comme l'épiderme viable, alors que c'était le cas pour la formulation avec une concentration élevée de phospholipides (15 mg / mL), bien que l'EE% était d'environ 55%. Le double déplacement de solvant est une technique très prometteuse de préparation de vésicules lipidiques, capable de produire une population monodisperse d'échelle nanométrique. Cette méthode n'est que légèrement impactée lors d'une transposition d'échelle et serait donc facile à mettre en oeuvre à l'échelle industrielle. Cette méthode a été conçue dès le début pour utiliser des solvants favorisant la pénétration cutanée mais l'étendue de ces applications reste à explorer / Psoriasis is an auto-immune and chronic skin disease. Psoriatic arthritis is the main complication which is very disabling for patients. This pathology still remains incurable to date. The currently psoriasis indicated medicines use is limited by their side effects which are dose and use duration dependent. The aim of this work was to develop lipid based nanocarriers for skin targeting, especially the viable epidermis which is the main site of psoriasis physiopathology but also the dermis and beyond in order to reach the damaged articulations. Thanks to a new technique we developed and optimized called the double solvent displacement, based on a two-step phospholipid organization, we prepared diclofenac and cyclosporine A loaded lipid vesicles. Then, we evaluated their potential to cross the skin and target the skin layers of interest. After a systematic study to optimize preparation parameters, diclofenac and cyclosporine A loaded lipid vesicles displayed an encapsulation efficiency (EE %) between 50% and 90% respectively, according to the phospholipid concentration. After in vitro skin studies, we observed that the formulation containing the lower phospholipid concentration (8.5 mg/mL) allowed to encapsulate more than 80% of diclofenac and also to target the dermis and beyond. The formulation of cyclosporine A loaded lipid vesicles which encapsulates the higher amount (around 80%) is also the one containing the lower phospholipid concentration. Unlike to diclofenac, this formulation was not the better to target the viable epidermis whereas the formulation with the higher phospholipid concentration (15 mg/mL) was even though the EE% was of around 55%. The double solvent displacement is a very promising technique of lipid vesicle preparation, capable to produce monodisperse population of nanoscale carriers. This method is hardly impacted during scale-up and would be easy to implement at an industrial scale. This method was designed from the beginning to use skin penetration enhancer solvents but the scope of its applications still remains to be explored

Bergström, A Utvärdering av hudvänliga lösningsmedel för ökad löslighet av NSAID i topikala formuleringar. Examensarbete i Farmakologi 15 poäng. Malmö Universitet: Fakulteten för Hälsa och Samhälle, Institutionen för Biomedicinsk Vetenskap, 2019.Introduktion Smärta har behandlats med topikala eller transdermala läkemedel i många år, men det är en utmaning att uppnå höga koncentrationer som kan transporteras över huden. För att kunna ersätta användandet av opioider vid behandling av måttlig till allvarlig smärta behövs mer effektiva formuleringar av transdermala läkemedel. Målet med denna studie var att undersöka möjligheten att öka mängden aktiv substans som transporteras över huden. För detta ändamål, bestämdes lösligheten hos diklofenak i olika lösningsmedel. Vidare bestämdes transporten av diklofenak över silikonmembran från dessa lösningsmedel med hjälp av Franz celler.Metod Lösligheten hos diklofenak studerades vid 32ºC i vatten, fosfatbuffrad saltlösning (PBS), saltlösning, polyetylenglykol (PEG) 400, polyetylenglykol (PEG) 1500 (60 vikt % i vatten), glycerol, propylenglykol, 1-propanol och 2-propanol. Diffusion hos diklofenak över silikonmembran från nämnda formuleringarna, inklusive Voltaren Gel som jämförelse, studerades med hjälp av Franzceller under sex timmar. För både löslighet- och diffusionsexperimenten bestämdes koncentrationen av diklofenak med en analysmetod baserad på UV-spektrofotometri.Resultat Lösligheten av diklofenak var högst i PEG 400 och propylenglykol med ungefär 40 vikt %. Den lägsta lösligheten uppmättes i 2-propanol med ca 1 %. I diffusionsstudierna kunde diklofenak enbart detekteras i receptorkammaren, dvs diklofenas transporterades över membranet, hos de formuleringar som innehöll enbart vatten eller Voltaren.Diskussion Resultatet av löslighetstesterna kunde förklaras genom att ta de kemiska och fysikaliska egenskaperna hos den olika lösningsmedlen som användes i beaktande samt genom att använda begrepp som utsaltningseffekt och vätedonatorer/acceptorer. Resultaten av diffusionsstudierna var ofullständiga men då enbart ett begränsat antal experiment kunde utföras inom ramen för detta arbete behöver resultaten vidare styrkas.Nyckelord: Diffusion, diklofenak, Franz cell, löslighet, transdermal / Bergström, A Evaluation of skin-friendly solvents for increased solubility of a model NSAID in topical formulations. Degree project in Pharmacology 15 credits. Malmö University: Faculty of Health and Society, Department of Biomedical Science, 2019.Introduction Pain has been treated with topical or transdermal drugs for many years, but the concentration of active substance that can be transported over the skin remains low. To be able to substitute the use of opioids in treatment of moderate to severe pain, more efficient formulations of transdermal drugs are needed. The aim of this study was to investigate the possibility to increase the concentration of diclofenac in topical formulations. For this reason, the solubility of diclofenac in different skin-friendly solvents was determined. In addition, the diffusion of diclofenac across silicone membranes from these solvents was investigated using Franz cells.Methods The solubility of diclofenac was studied at 32ºC in water, phophate buffered saline solution (PBS), saline solution, polyethylene glycol (PEG) 400, polyethylene glycol (PEG) 1500 (60 wt% in water), glycerol, propylene glycol, 1-propanol and 2-propanol. The diffusion of diclofenac over silicon membrane, used as a model for skin membranes, from six formulations, including Voltaren for comparison, was studied using Franz diffusion cells over six hours. Both for the solubility and diffusion experiments, the concentration of diclofenac was determined by an analytical method based on UV-spectroscopy.Results The solubility of diclofenac was highest in PEG 400 and propylene glycol with approximately 40 wt. %. The lowest solubility was seen in 2-propanol with approximately 1 %. In the diffusion study, only the formulation containing water as solvent and Voltaren gel resulted in detection of dicofenac in the receptor chamber, i.e. transported over the membrane in the time frame studied.Discussion The results of the solubility experiments can be rationalized based on the chemical and physical properties of the solvents and by considering concepts such as the salting-out efffect and appropriate number of hydrogen bond donors and acceptors. The results of the diffusion studies were inconclusive and since only a limited number of experiments could be performed within the scope of this work, the results need to be authenticated.Keywords: Diclofenac, diffusion, Franz cell, solubility, transdermal

Heterogenous photocatalysis using titanium dioxide seems to be a promising method for disposal xenobiotics from the environment. The aim of this diploma thesis is the study of degradation of selected xenobiotics and biologically active substrances applying this method. Theoretical part of diploma thesis deals with the principals of heterogenous photocatalysis by means of a semiconductor TiO2 and the examples of its possible application are mentioned too. The compounds which could be appropriate for a study of degradation were selected from the group of pharmaceuticals and pesticides. The properties of target substances and their environmental impact were described. Furthermore, a bibliographic search focused on the possibilities of their analytical determination was conducted. The experimental part of the thesis describes the experiments with photocatalyst in a form of powder as well as with immobilized photocatalyst in thin layer on a carrier. Identification and quantification of analytes was realized by high performance liquid chromatography with mass spectrometic detection.

Bis zu 95 % der Wirkstoffe von Arzneimittel der Humanmedizin werden unverändert ausgeschieden oder gelangen über die täglichen Hygiene in den Wasserkreislauf. Die meisten Substanzen werden sehr schnell und vollständig abgebaut oder liegen in Konzentrationen vor, in denen sie keine Gefährdung für die Umwelt und den Menschen darstellen. Im Gegensatz dazu gibt es aber auch Substanzen, die nur sehr schwer abgebaut werden können (persistent sind) und für die bereits negative Langzeiteffekte in umweltrelevanten Konzentrationen für Tiere nachgewiesen wurden. Ein Beispiel dafür ist der schmerzstillende Wirkstoff Diclofenac. Aus diesem Grund und wegen der guten Kenntnislage hinsichtlich Vorkommen, Abbauprodukte und Analytik wurde Diclofenac als Referenzverbindung für die Experimente im Rahmen dieses Projekts verwendet. Aufgrund der geringen Konzentration von Diclofenac in Wasser und der chemischen Stabilität von Diclofenac sowie einiger anderer Spurenstoffe sind herkömmliche Wasserbehandlungsverfahren, wie sie derzeit in Kläranlangen verwendet werden, ineffizient oder zu teuer. Deshalb gibt es zahlreiche Bemühungen, alternative und umweltschonende Behandlungsverfahren zur Entfernung von Arzneimittelrückständen aus Wasser zu entwickeln, die einen vollständigen Abbau der Rückstände ermöglichen. Idealerweise sollten technische Lösungen zur Verfügung stehen, die gegebenenfalls in jedem Land der Erde einsetzbar wären. Der in diesem Projekt verfolgte Ansatz zur Entwicklung fotokatalytischer Schichten, die idealerweise bereits bei Tageslicht eine ausreichend hohe Aktivität aufweisen, ist besonders interessant, da es nach Optimierung weder des zusätzlichen Einsatzes von Chemikalien noch des Einsatzes von Energie bedarf. So werden durch die Bestrahlung des Katalysators (z.B. ZnO, TiO2) mit künstlichem UV-Licht, perspektifisch aber mit UV-A-Strahlung der Sonne sowohl Wasser als auch Luftsauerstoff zu reaktiven Hydroxylradikalen umgesetzt, die letztendlich die unspezifischen Spaltung organischer Verbindungen im Wasser bewirken. Voraussetzung für die Optimierung hinsichtlich katalytischer Aktivität und Empfindlichkeit gegenüber Tageslicht ist ein Herstellungsverfahren, das die Optimierung der fotokatalytischen Schichten bezüglich verschiedener Parameter (optimale Größe, enge Größenverteilung, Möglichkeit der einfachen Dotierung, Verhinderung der Agglomeration bei gleichzeitiger dauerhafter Immobilisierung) erlaubt. Diesbezüglich besonders aussichtsreich ist die Verwendung von hoch geordneten bakteriellen Hüllproteinen sogenannten „surface-layer“ (S-Layer)-Proteinen, die sowohl eine einfache Herstellung von fotokatalytisch aktiven Nanopartikeln aus verschiedenen Elementen erlauben, als auch zur Beschichtung verschiedener Materialien geeignet sind. Ein Ziel im Projekt ist die Herstellung von reinen und dotierten ZnO und TiO2-Nanopartikeln zur Eliminierung von Diclofenac aus Wasser (siehe Abbildung 1). Dabei dienen S-Layer verschiedener Bakterien und damit Proteinschichten mit unterschiedlichen Symmetrien, Gitterabständen und Porengröße als Template für die Herstellung von Nanopartikeln verschiedener aber definierter Größe. Darüber hinaus werden die S-Layer im Projekt als Trenn- und Immobilisierungsschicht für die erzeugten Nanopartikel genutzt. Letzteres vor allem zur Verhinderung einer Agglomeration und des Austrags der Nanopartikel, was beides einen Verlust der katalytischen Aktivität entsprechender Schichten bedeuten würde. Als Träger werden im Rahmen des Projekts verschiedene in technischen Anwendungen genutzte Materialien dahin gehend überprüft, in wie weit sich S-Layer darauf abscheiden lassen und stabile Schichten ausbilden und darauf aufbauend ein Trägermaterial für die Herstellung fotokatalytisch aktiver Beschichtungen ausgewählt. Gleichzeitig war es Ziel des Projektes, die Biomassegewinnung hinsichtlich eines Upscalings und hinsichtlich der Kosten zu optimieren. Ausgehend von dieser konkreten wissenschaftlichen Fragestellung war es auch Ziel des Projektes, ein verwertungsorientiertes Netzwerk aufzubauen. Dies vor allem zur Sicherung der Fortentwicklung der neuen Materialien und der Weiterführung der begonnenen Arbeiten in dem konkreten Forschungsgebiet mit dem Ziel der Entwicklung eines marktreifen Produktes aber auch zur Etablierung einer dauerhaften Kooperation zwischen den verschiedenen Forschungs- und Industriepartnern. Diese Ziele sollten insbesondere über eine Vernetzung von Instituten innerhalb der Leibniz-Gemeinschaft, weiteren regionalen und überregionalen Forschungseinrichtungen sowie Industriepartnern erreicht werden. Die sehr gute gerätetechnische Ausstattung, die im vorliegenden Fall über die Projektmittel erreicht wurde, war nicht nur Voraussetzung zur Durchführung der geplanten Forschungs- und Entwicklungsarbeiten und zur Herstellung von Materialien im kleintechnischen Maßstab, sondern erhöhte auch die Attraktivität des Teams als Projektpartner weiter und nachhaltig. Erfahrungen aus dem Projekt und dem Prozess der Netzwerkbildung sollen insbesondere unter Einbeziehung der Geschäftsstelle der Leibniz-Gemeinschaft zur Entwicklung eines Prozessleitfadens für die Bildung von Verwertungs- und Transfernetzwerken innerhalb der Leibniz-Gemeinschaft genutzt werden.

Over the last decade, three species of Gyps vultures on the Asian subcontinent have declined dramatically in population numbers, some as much as 97 to 99%. Although the initial cause was believed to be infectious, it was later shown to be due to an inadvertent exposure to diclofenac via the food chain. In order to protect the remaining wild vultures, diclofenac needed to be removed from the food chain. Unfortunately the Indian government was reluctant to ban diclofenac until an alternate veterinary non-steroidal anti-inflammatory drug (NSAID) that was both safe in vultures and effective in cattle could be identified. Although meloxicam was tentatively identified as this drug, toxicity testing still needed to be undertaken. Using a previously validated model, two studies were undertaken to determine the acute toxic effect of diclofenac in vulture as well as to ascertain if the drug had the potential to accumulate. In the first study, meloxicam in formulation was shown to be safe as a single oral dose up to 2mg/kg in African White Backed-Vultures (Gyps africanus). To further demonstrate the safety of food borne meloxicam, vultures were exposed to meat rich in meloxicam residues, with once again no signs of toxicity being evident. In the second study the drugs ability to accumulate was evaluated pharmacokinetically in Cape Griffon Vultures (Gyps corprotheres). From this study meloxicam was shown to have a very short half-life of elimination, making it unlikely that the drug could be a cumulative toxin. This was subsequently confirmed clinically by the absence of toxicity in birds receiving repeated doses of meloxicam. Although meloxicam was shown to be adequately safe, the safety of other veterinary NSAIDs still required elucidation. While further testing in vultures would have been possible, the small population size of the various vulture species made this unethical. Therefore a surrogate species needed to be identified. With the domestic chicken (Gallus domesticus) being commonly available, attempts were made to validate the chicken as a model. Although the dosed chickens did show similar toxicity patterns from clinical pathology to histopathology, a major problem was their higher tolerance making it impossible to use them as a surrogate. It was, however, concluded that the domestic chicken may be used in mechanistic studies in an attempt to establish an in vitro model. From the mechanistic studies both diclofenac and meloxicam were directly toxic to chicken and vulture renal tubular epithelial cells following 48h of incubation. It was later shown that this toxicity was associated with an increased production of reactive oxygen species (ROS), which could be temporarily ameliorated by pre-incubation with uric acid due to its anti-oxidant activity. When cultures were incubated with either drug for only two hours, meloxicam showed no toxicity in contrast to the cellular toxicity present for diclofenac. In both cases no increase in ROS production was evident. In addition diclofenac influenced the excretion of uric acid by interfering with p-amino-hippuric acid channels. The effect on uric acid excretion persisted after the removal of the diclofenac. It was therefore concluded that vulture susceptibility to diclofenac results from a combination of an increase in cellular ROS, a depletion of intracellular uric acid concentration and most importantly the drug’s long half-life in the vulture. Unfortunately the importance of the drug’s half-life in the toxicodynamics makes it unlikely that in vitro testing will be possible. / Thesis (PhD (Paraclinical Sciences))--University of Pretoria, 2007. / Paraclinical Sciences / unrestricted

Water from the Llobregat is used to supply a significant part of the city of Barcelona. At the same time, 60 wastewater treatment plants discharge into this basin. Two field campaigns conducted in the Llobregat Catchment detected more than 80 pharmaceu-ticals in the water. Therefore, it is clear that water quality in Llobregat is a potential concern. A GIS hydrology water quality model has been applied in order to predict the concentrations of one of the pharmaceuticals, diclofenac, in the catchment. Con-sumption, excretion, and degradation data has been studied to calibrate the model. This exercise proves that it is relatively straightforward to predict the concentrations of new and emerging contaminants at basin scale. Nonetheless, the limited and inac-curate available data was a relevant obstacle in this modelling process.

A double-blind, placebo controlled research technique was used to determine the effects of two non-steroidal anti-inflammatory drugs, meclofenamate and diclofenac, in combination with physiotherapy treatment, on the rate and extent of healing of acute hamstring muscle tears. Sixty patients were recruited and treated at No's 1 and 2 Military Hospitals in Voortrekkerhoogte and Wynberg, Cape Town, respectively. Patients were randomly allocated to one of three treatment groups: meclofenamate, diclofenac and placebo. Patient assessments were performed on days 1, 3 and 7 of the 7-day study period. These assessments included pain assessment (visual analogue scale), swelling measurement (thigh circumference measurement at the site of the muscle tear) and muscle performance test (Cybex isokinetic dynamometer and data reduction computer). All patients received physiotherapy treatment on all 7 days of the study. This comprised early rest, ice, compression and elevation (RICE), and later, ultrasound and deep transverse friction massage. An intensive regime of strengthening and stretching exercises was used throughout the study, beginning with stretching and isometric exercises gradually moving onto isotonic exercises and aerobic exercise including swimming, running and cycling. No competitive sport was allowed during the study period. Statistical significance was determined using the analysis-of-variance (ANOVA) test with an acceptance level of p<0.05. No differences in pain, swelling or muscle performance were demonstrated between the three treatment groups. In terms of the pain and swelling assessments, the injuries did not appear to be very severe. Accordingly, the groups were divided into severe and non-severe sub-groups and statistical significance was determined using the ANOVA test with an acceptance level of p<0.05. A significant difference was found in the severe hamstring injury sub-group. In this group, pain reduction was greater in the placebo group than in the meclofenamate group on day 7. There were no other significant differences found in this sub-group analysis. Relatively few side effects were encountered, and those encountered were mild. No patients were withdrawn from the study as a result of these adverse events. Drowsiness and gastro-intestinal disturbance were the most common side effects reported. In conclusion, the study found that no benefit was gained from the use of meclofenamate or diclofenac in combination with physiotherapeutic modalities as compared to the use of physiotherapeutic modalities on their own. Thus, the widespread use of NSAIDs in the treatment of acute muscle injuries may not be justified.

Pharmaceuticals in aquatic environments have been put under increasing scientific scrutiny as they are frequently found as contaminants in natural waters, often entering via effluent water containing pharmaceutical residue from human excretion. Diclofenac is a frequently found non-steroidal anti-inflammatory drug [NSAID] in waters that has been shown to cause both acute and chronic effects on various aquatic organisms. A common method to assess the effects of sub-lethal exposures has been behavioral experiments, yet these tests are often not considered in regulatory decision-making. This study aimed to evaluate if diclofenac can cause behavioral changes in fish through a meta-analysis of existing literature. A total of 372 studies, identified from six different databases, were reviewed. A random-effects model was applied on four studies where behaviors acting as proxies for fish activity were measured in response to diclofenac exposure. It was found that diclofenac does not seem to affect the activity in fish in neither light nor dark conditions, with one potential exception at high exposure levels (&gt;100 μg/L) in light conditions causing decreased activity. A comparison using available monitoring data in waters from national databases (including sampling between years 2005 and 2021) was used to illustrate that diclofenac concentrations in Sweden, and globally, do not exceed this latter value. Therefore, it appears unlikely that diclofenac will influence the activity in fish.

Diclofenac (DCF) and other emerging contaminants have been found in environments worldwide. These contaminants may enter the environment due to the application of treated wastewater, biosolids and direct excrement related to veterinary application. Leakage from the soils toward the groundwater is largely controlled by sorption and microbial degradation. Most studies on the environmental fate of DCF have focused on degradation during wastewater treatment processes. However, little is known about their behavior in soil. In this study, the combined effect of adsorption and degradation of diclofenac has been investigated in four (4) 24 ft3 agricultural soil-filled beds designed to mimic natural vegetated soil environments, enhanced via controlled wetting and drying cycles. Contour bund installation on slopes of 5, 10, 15 and 20° were mimicked in the beds. Results showed that the soil environment was a strong inhibitor to the leaching of DCF through the soil. Saturating slopes via contour bund application however can lead to landslides that may impact structures and human life. A feasible contour bund installation site was investigated and found that 20° slopes under saturated conditions resulted in an unsafe factor of safety and is not encouraged as a solution for stormwater management. The effect of contour bund application on slopes under 15° at the installation site can potentially increase removal of emerging contaminants, thereby protecting groundwater resources without endangering life or property.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, anti-pyretic and anti-inflammatory properties in both human and veterinary patients. Topical ophthalmic NSAIDs are commonly employed in the management of intraocular inflammation (uveitis), corneoconjunctival inflammatory disease and pre-operatively to prevent intraoperative miosis during cataract surgery. Despite their routine application in these clinical scenarios, little is known regarding the corneal penetration and relative anti-inflammatory efficacy of the available topical ophthalmic NSAIDs in the dog. Decisions regarding which of these agents to employ are therefore based upon factors such as cost and ease of acquisition as opposed to established efficacy. Objectives: To investigate the relative intraocular penetration and anti-inflammatory efficacy of two commonly utilized topical ophthalmic NSAIDs in dogs, diclofenac 0.1% and ketorolac 0.5%. Animals: Twenty-two client owned dogs (22 operated eyes) presenting to the VTH ophthalmology service for routine cataract surgery for mature or hypermature cataract. Methods: Subjects were randomized to be treated with either topical ketorolac 0.5% or topical diclofenac 0.1% ophthalmic solutions at specified times in the 24-hour period pre-operatively. Aqueous humor samples were obtained intra-operatively and stored for subsequent evaluation of drug concentrations and prostaglandin E2 (PGE2) concentrations via ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and enzyme-linked immunoassay (ELISA) analysis, respectively. Results: Median aqueous humor drug concentrations were significantly higher in dogs treated with ketorolac 0.5% (1311.6 ng/mL) compared to those treated with diclofenac 0.1% (284.9 ng/mL). There was no significant difference in aqueous humor PGE2 concentrations between the two treatment groups. No significant association was determined between aqueous humor drug concentration and PGE2 concentration. There was no significant association between diabetic status and aqueous humor drug concentration or PGE2 concentration in either group. Conclusions and clinical importance: This study suggests that topical ketorolac 0.5% and diclofenac 0.1% are efficacious in decreasing aqueous humor PGE2 concentrations and are equally suitable for use based on their comparable anti-inflammatory profiles. The results of these assays provide clinically relevant information regarding intraocular penetration and anti-inflammatory efficacy of these medications in dogs with cataract. / Master of Science / Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, anti-pyretic and anti-inflammatory properties in both human and veterinary patients. Topical ophthalmic NSAIDs are commonly employed in the management of intraocular inflammation (uveitis), corneoconjunctival inflammatory disease and pre-operatively to prevent intraoperative miosis during cataract surgery. Despite their routine application in these clinical scenarios, little is known regarding the intraocular penetration and relative anti-inflammatory efficacy of the available topical ophthalmic NSAIDs in the dog. Decisions regarding which of these agents to employ are therefore based upon factors such as cost and ease of acquisition as opposed to established efficacy. Efficacy of topical anti-inflammatory medications in controlling intraocular inflammation is primarily related to the ability of the medication to penetrate the cornea and its efficacy at suppressing inflammatory mediators. The purpose of this study, therefore, is to investigate the relative intraocular penetration and anti-inflammatory efficacy of two commonly utilized topical ophthalmic NSAIDs in dogs, diclofenac 0.1% and ketorolac 0.5%. Twenty-two dogs presenting to the VTH ophthalmology service for routine cataract surgery with the presence of a mature or hypermature cataract were enrolled in a prospective, randomized clinical trial. Subjects were treated with either topical ketorolac 0.5% or topical diclofenac 0.1% ophthalmic solutions at specified times in the 24-hour period pre-operatively. Aqueous humor samples were obtained intra-operatively and stored for subsequent evaluation of drug concentrations (n=22) and prostaglandin E2 (PGE2) concentrations (n=19) via ultra performance liquid chromatography (UPLC) and enzyme-linked immunoassay (ELISA) analysis, respectively. Treatment with topical ketorolac 0.5% resulted in higher median aqueous humor drug concentrations when compared to treatment with diclofenac 0.1% (1311.6 ng/mL vs. 284.9 ng/mL). However, there was no significant difference in anti-inflammatory efficacy when comparing PGE2 concentrations between the two groups. Furthermore, no significant association was determined when drug concentration was directly compared with PGE2 concentration. The results of these assays suggest that topical ketorolac 0.5% and diclofenac 0.1% are equally suitable for use based on their comparable anti-inflammatory profiles, and provides clinically relevant information regarding intraocular penetration and anti-inflammatory efficacy of these medications in dogs with cataract.