The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Jonathan N. King - One of the best experts on this subject based on the ideXlab platform.
-
clinical safety of Robenacoxib in cats with chronic musculoskeletal disease
Journal of Veterinary Internal Medicine, 2021Co-Authors: Jonathan N. King, Wolfgang Seewald, Gabriele Friton, Derek Adrian, Sophie Forster, Duncan B X LascellesAbstract:BACKGROUND Evaluate the clinical safety of Robenacoxib in cats with chronic musculoskeletal disease (CMSD). ANIMALS Four hundred forty-nine client-owned cats with CMSD. METHODS Pooled analysis of safety variables from 4 prospective randomized blinded clinical trials of Robenacoxib (n = 222) versus placebo (n = 227), administered orally once daily for 4 to 12 weeks. Safety was evaluated from reported adverse events (AEs) and abnormalities detected on hematology and serum and urine chemistry analyses. RESULTS The number of cats with at least 1 AE was not significantly different (P = .15) with Robenacoxib (n = 106, 47.8%) compared to placebo (n = 93, 41.0%). The relative risk of at least 1 AE (incidence Robenacoxib/placebo) was 1.15 (95% confidence interval 0.93-1.43). There was no significant difference between groups in the number of clinical signs (range, 0-9) per cat (P = .23). Serum creatinine concentrations were higher during Robenacoxib administration compared to placebo (+4.36 μmol/L, 95% confidence interval 0.21-8.50), but no related adverse clinical effects were detected. In the subgroup of 126 cats with evidence of chronic kidney disease, the relative risk of at least 1 AE (Robenacoxib/placebo) was 1.09 (95% confidence interval 0.78-1.52, P = .61). CONCLUSIONS AND CLINICAL IMPORTANCE Robenacoxib was not associated with increased risk of AEs compared to placebo when administered for 4 to 12 weeks to cats with CMSD. The generalizability of the results to general practice is limited by the fact that cases with severe and uncontrolled concomitant diseases were not included.
-
determination of the route of excretion of Robenacoxib onsior in cats and dogs a pilot study
Journal of Veterinary Pharmacology and Therapeutics, 2021Co-Authors: Jonathan N. King, Martin JungAbstract:The objective of the studies was to determine the route of excretion, faecal or urinary, of the nonsteroidal anti-inflammatory drug (NSAID) Robenacoxib (Onsior™) in cats and dogs. The studies employed a two-part crossover design in 4 beagle dogs (2 female and 2 male, age 36-41 months and body weight 9.0-10.3 kg) and a parallel group comparison of two groups each of 3 domestic short-hair cats (2 female and 4 castrated male, age 35-73 months and body weight 3.0-5.7 kg). Animals were administered single doses of 1 (dog) or 2 (cat) mg/kg of [14 C]-Robenacoxib by intravenous (IV) and oral routes. Venous blood samples were taken and analysed for Robenacoxib concentration. Faeces and urine were collected for 4 (cats) or 7 (dogs) days and analysed for radioactivity. Robenacoxib was eliminated rapidly from blood (≤ 8 hr). In dogs, expressed as the percentage of the administered dose and adjusted so that faecal plus urine recovery was 100%, the mean (SD) excretion in faeces and urine was, respectively, 64.6% (4.30) and 35.4% (4.3) after IV and 66.7% (6.9) and 33.3% (6.9) after oral administration. The respective values in cats, in faeces and urine, were 72.5% (4.6) and 27.5% (4.6) after IV and 78.5% (2.6) and 21.5% (2.6) after oral administration. In conclusion, excretion of systemically available Robenacoxib in cats and dogs was mixed via both faeces and urine, but predominately faecal (~64.6% in dogs and ~72.5% in cats) and assumed to be via biliary excretion.
-
Robenacoxib shows efficacy for the treatment of chronic degenerative joint disease associated pain in cats a randomized and blinded pilot clinical trial
Scientific Reports, 2021Co-Authors: Derek Adrian, Jonathan N. King, Stephen King, Rudolph S Parrish, Steven C Budsberg, Margaret E Gruen, Duncan B X LascellesAbstract:The main objective of this pilot clinical trial was to evaluate outcome measures for the assessment of the nonsteroidal anti-inflammatory drug (NSAID) Robenacoxib in cats with degenerative joint disease-associated pain (DJD-pain). Otherwise healthy cats (n = 109) with DJD-pain entered a parallel group, randomized, blinded clinical trial. Cats received placebo (P) or Robenacoxib (R) for two consecutive 3-week periods. Treatment groups were PP, RR, and RP. Actimetry and owner-assessment data were collected. Data were analyzed using mixed-effects and generalized mixed-effects linear models. Activity data showed high within-cat and between-cat variability, and 82.4% of the values were zero. Compared to placebo, mean total activity was higher (5.7%) in Robenacoxib-treated cats (p = 0.24); for the 80th percentile of activity, more Robenacoxib-treated cats had a > 10% increase in activity after 3 (p = 0.046) and 6 weeks (p = 0.026). Robenacoxib treatment significantly decreased owner-assessed disability, (p = 0.01; 49% reduction in disability; effect size ~ 0.3), and improved temperament (p = 0.0039) and happiness (p = 0.021) after 6 weeks. More Robenacoxib-treated cats were successes at 6 weeks (p = 0.018; NNT: 3.8). Adverse effect frequencies were similar across groups. Results identified suitable endpoints for confirmatory studies, while also indicating efficacy of Robenacoxib in cats with DJD-pain.
-
Efficacy and safety of oral Robenacoxib (tablet) for the treatment of pain associated with soft tissue surgery in client-owned dogs
BMC Veterinary Research, 2017Co-Authors: Gabriele Friton, Stephen King, Caryn Marie Thompson, Daniela Karadzovska, Jonathan N. KingAbstract:Background Non-steroidal anti-inflammatory drugs (NSAIDs) have been proven to be effective in controlling peri-operative pain in dogs. Robenacoxib is an NSAID with high selectivity for the cyclooxygenase (COX)-2 isoform. The objective of this study was to assess the efficacy and safety of an oral tablet formulation of Robenacoxib in client-owned dogs undergoing soft tissue surgery. The study was a prospective, multi-center, randomized, masked, placebo-controlled, parallel-group clinical trial. A total of 239 dogs were included and randomly allocated in a 1:1 ratio to receive either Robenacoxib or placebo. Each dog received an oral tablet administration of either Robenacoxib, at a target dose of 2 mg/kg, or placebo once prior to surgery and for two additional days post-operatively. All dogs also received a pre-anesthetic dose of 0.2 mg/kg butorphanol (intravenous or intramuscular). Pain assessments were performed using the short form of the Glasgow Composite Measure Pain Scale. Robenacoxib was compared to the placebo group on a success/failure basis. Treatment failure was defined as the need for rescue therapy to control post-operative pain. Results Significantly ( P = 0.019) more dogs administered Robenacoxib were considered treatment successes (89 of 116, 76.72%) compared to dogs given placebo (74 of 115, 64.35%). The percentage of treatment failure was therefore 23.28% in the Robenacoxib and 35.65% in the placebo group. The least squares mean total pain scores were significantly different between groups and in favor of Robenacoxib at 3 and 5 hours ( P < 0.05) and 8 hours post-extubation ( P < 0.01). Pain at the surgery sites (response to touch) was also significantly improved at 3, 5 and 8 hours post-extubation in dogs receiving Robenacoxib versus placebo ( P < 0.01). In addition, a significant overall improvement in posture/activity was revealed with Robenacoxib having lower scores versus placebo ( P < 0.01). No significant differences between the Robenacoxib and placebo groups in the frequency of reported adverse events were observed. Conclusions Robenacoxib by oral (tablet) administration was effective and well tolerated in the control of peri-operative pain and inflammation associated with soft tissue surgery in dogs.
-
efficacy and safety of oral Robenacoxib tablet for the treatment of pain associated with soft tissue surgery in client owned dogs
BMC Veterinary Research, 2017Co-Authors: Gabriele Friton, Stephen King, Caryn Marie Thompson, Daniela Karadzovska, Jonathan N. KingAbstract:Non-steroidal anti-inflammatory drugs (NSAIDs) have been proven to be effective in controlling peri-operative pain in dogs. Robenacoxib is an NSAID with high selectivity for the cyclooxygenase (COX)-2 isoform. The objective of this study was to assess the efficacy and safety of an oral tablet formulation of Robenacoxib in client-owned dogs undergoing soft tissue surgery. The study was a prospective, multi-center, randomized, masked, placebo-controlled, parallel-group clinical trial. A total of 239 dogs were included and randomly allocated in a 1:1 ratio to receive either Robenacoxib or placebo. Each dog received an oral tablet administration of either Robenacoxib, at a target dose of 2 mg/kg, or placebo once prior to surgery and for two additional days post-operatively. All dogs also received a pre-anesthetic dose of 0.2 mg/kg butorphanol (intravenous or intramuscular). Pain assessments were performed using the short form of the Glasgow Composite Measure Pain Scale. Robenacoxib was compared to the placebo group on a success/failure basis. Treatment failure was defined as the need for rescue therapy to control post-operative pain. Significantly (P = 0.019) more dogs administered Robenacoxib were considered treatment successes (89 of 116, 76.72%) compared to dogs given placebo (74 of 115, 64.35%). The percentage of treatment failure was therefore 23.28% in the Robenacoxib and 35.65% in the placebo group. The least squares mean total pain scores were significantly different between groups and in favor of Robenacoxib at 3 and 5 hours (P < 0.05) and 8 hours post-extubation (P < 0.01). Pain at the surgery sites (response to touch) was also significantly improved at 3, 5 and 8 hours post-extubation in dogs receiving Robenacoxib versus placebo (P < 0.01). In addition, a significant overall improvement in posture/activity was revealed with Robenacoxib having lower scores versus placebo (P < 0.01). No significant differences between the Robenacoxib and placebo groups in the frequency of reported adverse events were observed. Robenacoxib by oral (tablet) administration was effective and well tolerated in the control of peri-operative pain and inflammation associated with soft tissue surgery in dogs.
P. Lees - One of the best experts on this subject based on the ideXlab platform.
-
Additional file 1 S1: of Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney
2015Co-Authors: Ludovic Pelligand, P. Lees, W Seewald, N. Suemanotham, J. King, H. Syme, K. Smith, J. ElliottAbstract:PK-PD integration of Robenacoxib and ketoprofen (description of data): estimation of the average duration of COX-1 and COX-2 inhibition achieved with Robenacoxib once a day (RSID), Robenacoxib twice a day (RBID) and ketoprofen (KET) using data from the literature. (DOCX 424 KB
-
differential pharmacokinetics and pharmacokinetic pharmacodynamic modelling of Robenacoxib and ketoprofen in a feline model of inflammation
Journal of Veterinary Pharmacology and Therapeutics, 2014Co-Authors: Ludovic Pelligand, J N King, J. Elliott, Pierre-louis Toutain, Victor Hormazabal, P. LeesAbstract:Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of Robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B2 concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E2 concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For Robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and Robenacoxib, respectively. Both drugs reduced exudate PGE2 concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB2 between 4 min and 24 h, whereas suppression was mild and transient with Robenacoxib. In vivoIC50COX‐1/IC50COX‐2 ratios were 66.9:1 for Robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood.
-
Differential pharmacokinetics and pharmacokinetic/pharmacodynamic modelling of Robenacoxib and ketoprofen in a feline model of inflammation
Journal of Veterinary Pharmacology and Therapeutics, 2014Co-Authors: Ludovic Pelligand, J N King, J. Elliott, Pierre-louis Toutain, Victor Hormazabal, P. LeesAbstract:Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of Robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B2 concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E2 concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For Robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and Robenacoxib, respectively. Both drugs reduced exudate PGE2 concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB2 between 4 min and 24 h, whereas suppression was mild and transient with Robenacoxib. In vivoIC50COX‐1/IC50COX‐2 ratios were 66.9:1 for Robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood.
-
effects of route of administration and feeding schedule on pharmacokinetics of Robenacoxib in cats
American Journal of Veterinary Research, 2013Co-Authors: J N King, Wolfgang Seewald, Martin Jung, Max P Maurer, Vincent Schmid, P. LeesAbstract:Objective—To establish pharmacokinetics of Robenacoxib after administration to cats via the IV, SC, and oral routes. Animals—24 cats. Procedures—In a crossover design, Robenacoxib was administered IV, SC, and orally (experiment 1) and orally (experiment 2) to cats with different feeding regimens. Blood Robenacoxib concentrations were assayed, with a lower limit of quantification of 3 ng/mL. Results—In experiment 1, geometric mean pharmacokinetic values after IV administration of Robenacoxib were as follows: blood clearance, 0.44 L/kg/h; plasma clearance, 0.29 L/kg/h; elimination half-life, 1.49 hours; and volume of distribution at steady state (determined from estimated plasma concentrations), 0.13 L/kg. Mean bioavailability was 69% and median time to maximum concentration (Cmax) was 1 hour for cats after SC administration of Robenacoxib, whereas mean bioavailability was 49% and 10% and median time to Cmax was 1 hour and 30 minutes after oral administration to cats after food withholding and after cats we...
-
safety of oral Robenacoxib in the cat
Journal of Veterinary Pharmacology and Therapeutics, 2012Co-Authors: Jonathan N. King, W Seewald, R Hotz, E L Reagan, D R Roth, P. LeesAbstract:King, J. N., Hotz, R., Reagan, E. L., Roth, D. R., Seewald, W., Lees, P. Safety of oral Robenacoxib in the cat. J. vet. Pharmacol. Therap. 35, 290–300. The safety of Robenacoxib, a nonsteroidal anti-inflammatory drug with high selectivity for inhibition of the cyclooxygenase (COX)-2 isoform of COX, was investigated in the cat in two randomized, blinded, placebo-controlled, parallel-group studies. Robenacoxib was administered orally to healthy young domestic short-hair cats at dosages of 0 (placebo), 5 and 10 mg/kg once daily for 28 days (study 1) and at 0 (placebo), 2, 6 and 10 mg/kg twice daily for 42 days (study 2). The recommended minimum dosage for Robenacoxib tablets in cats is 1 mg/kg once daily (range 1–2.4 mg/kg). Relative to placebo treatment, no toxicologically significant effects of Robenacoxib were recorded in either study, based on general observations of health, haematological and clinical chemistry variables and urinalyses in life, and by post mortem organ weight, gross pathology and histopathology assessments. Pharmacokinetic–pharmacodynamic simulations indicated that all dosages of Robenacoxib were associated with marked inhibition of COX-2 at peak effect (median Imax 97.8–99.4% inhibition) with lesser inhibition of COX-1 (median Imax 26.8–58.3% inhibition). Inhibition of the COXs was short lasting, with >10% median inhibition persisting for 4.0 h for COX-2 and 1.5 h for COX-1. These levels of inhibition of COX-1 and COX-2 twice daily with Robenacoxib were not associated with any detectable toxicity, suggesting that, as previously described in dogs, the high safety index of Robenacoxib in cats may be related to a combination of its high COX-2 selectivity and short residence time in the central compartment.
Wolfgang Seewald - One of the best experts on this subject based on the ideXlab platform.
-
clinical safety of Robenacoxib in cats with chronic musculoskeletal disease
Journal of Veterinary Internal Medicine, 2021Co-Authors: Jonathan N. King, Wolfgang Seewald, Gabriele Friton, Derek Adrian, Sophie Forster, Duncan B X LascellesAbstract:BACKGROUND Evaluate the clinical safety of Robenacoxib in cats with chronic musculoskeletal disease (CMSD). ANIMALS Four hundred forty-nine client-owned cats with CMSD. METHODS Pooled analysis of safety variables from 4 prospective randomized blinded clinical trials of Robenacoxib (n = 222) versus placebo (n = 227), administered orally once daily for 4 to 12 weeks. Safety was evaluated from reported adverse events (AEs) and abnormalities detected on hematology and serum and urine chemistry analyses. RESULTS The number of cats with at least 1 AE was not significantly different (P = .15) with Robenacoxib (n = 106, 47.8%) compared to placebo (n = 93, 41.0%). The relative risk of at least 1 AE (incidence Robenacoxib/placebo) was 1.15 (95% confidence interval 0.93-1.43). There was no significant difference between groups in the number of clinical signs (range, 0-9) per cat (P = .23). Serum creatinine concentrations were higher during Robenacoxib administration compared to placebo (+4.36 μmol/L, 95% confidence interval 0.21-8.50), but no related adverse clinical effects were detected. In the subgroup of 126 cats with evidence of chronic kidney disease, the relative risk of at least 1 AE (Robenacoxib/placebo) was 1.09 (95% confidence interval 0.78-1.52, P = .61). CONCLUSIONS AND CLINICAL IMPORTANCE Robenacoxib was not associated with increased risk of AEs compared to placebo when administered for 4 to 12 weeks to cats with CMSD. The generalizability of the results to general practice is limited by the fact that cases with severe and uncontrolled concomitant diseases were not included.
-
safety evaluation of the interchangeable use of Robenacoxib in commercially available tablets and solution for injection in cats
BMC Veterinary Research, 2020Co-Authors: Mark C Heit, Wolfgang Seewald, Stephen King, Caryn Marie Thompson, Jay L Stallons, Celine E Toutain, Rainer HelbigAbstract:Robenacoxib (Onsior™) is a non-steroidal anti-inflammatory drug developed for canine and feline use for the control of pain and inflammation. It is available as both tablets and solution for injection. The objective of this study was to evaluate the safety of the interchangeable use of commercially available Robenacoxib formulations when administered to cats orally using 6 mg tablets and subcutaneously using a solution for injection containing 20 mg/mL. Thirty-four naive healthy 4-month old cats were enrolled in this 37-day study and were randomized to four groups (three Robenacoxib and one control). One Robenacoxib group received the maximum recommended dose (MRD) rate of each formulation, while the other two received two and three times this dose rate. The cats underwent three 10-day treatment cycles comprised of seven days of once daily oral administration followed by three days of subcutaneous administration. The third cycle was followed by an additional seven days of oral treatment. The control group received oral empty gelatin capsules or subcutaneous saline injections. Assessment of safety was based on general health observations, clinical observations, physical, ophthalmic, electrocardiographic and neurological examinations, clinical pathology evaluations, food consumption, body weight, and macroscopic and microscopic examinations. Blood samples were collected for toxicokinetic evaluation. Blood concentrations of Robenacoxib confirmed systemic exposure of all treated cats. All cats were in good health through study termination and there were no serious adverse events during the study. There were no changes in body weight, food consumption, ophthalmic, physical or neurological examinations during the study. Treatment-related abnormalities were of low occurrence at all doses and included injection site changes (transient edema with minimal or mild, subacute/chronic inflammation histologically) and prolongation of the QT interval. These findings were consistent with previously observed findings in studies with Robenacoxib administered separately orally or subcutaneously in cats. Thus, there were no adverse effects that could be attributed specifically to the interchangeable use of oral and injectable Robenacoxib. This 37-day laboratory study supports the safety of interchanging Robenacoxib injection at a daily dose of 2 mg/kg with Robenacoxib tablets at a daily dose of 1 mg/kg, or vice versa.
-
effect of benazepril Robenacoxib and their combination on glomerular filtration rate in cats
BMC Veterinary Research, 2016Co-Authors: Jonathan N. King, Wolfgang Seewald, Gabriele Friton, Alessandro Panteri, Melanie Graille, Cyril DesevauxAbstract:Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to evaluate the effects of benazepril, Robenacoxib and their combination in healthy cats. In each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n = 4 male and 4 female cats per group) in a parallel-group design. The groups received orally once daily for 7 days either placebo (control group), benazepril, Robenacoxib or benazepril plus Robenacoxib. In study 2, all groups received in addition 0.5 mg/kg furosemide twice daily by subcutaneous injection for 7 days. Benazepril, Robenacoxib and their combination were well tolerated as evidenced from lack of clinical signs and no negative effects on body weight, feed consumption and clinical chemistry, haematology and urinalysis variables. The primary endpoint of the study was the glomerular filtration rate (GFR), which was estimated from the plasma clearance of iohexol. In the absence of furosemide, GFR was significantly higher in cats receiving the combination of benazepril plus Robenacoxib compared to the other three groups, and was also significantly higher in females receiving only benazepril compared to the control. Administration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system, evidenced from increased plasma renin activity and plasma aldosterone concentrations. Compared to the control group in cats treated with furosemide, GFR was increased by benazepril (females only) but decreased by Robenacoxib (males only). Benazepril, Robenacoxib and their combination significantly inhibited the increase in plasma aldosterone induced by furosemide. The combination of benazepril and Robenacoxib was well tolerated and either increased or had a neutral effect on GFR in healthy cats without or with concomitant furosemide. The combination of benazepril and Robenacoxib reduced plasma aldosterone concentrations increased by furosemide. It is recommended to test the efficacy and safety of the combined use of benazepril and Robenacoxib in cats with clinical disease, notably proteinuric chronic kidney disease.
-
Robenacoxib versus meloxicam for the control of peri operative pain and inflammation associated with orthopaedic surgery in cats a randomised clinical trial
BMC Veterinary Research, 2015Co-Authors: Cindy Speranza, Wolfgang Seewald, Jerome M. Giraudel, Vincent Schmid, Jonathan N. KingAbstract:Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in veterinary medicine. Robenacoxib is a NSAID with high selectivity for the cyclo-oxygenase-2 enzyme. In this study, the efficacy and safety of Robenacoxib were evaluated in a prospective, randomised, active- and placebo-controlled masked clinical trial in 147 cats undergoing orthopaedic surgery. Cats were randomised into two treatment groups: Group 1, Robenacoxib (2 mg/kg) administered via subcutaneous (s.c.) injection before surgery, followed by Robenacoxib tablets (1–2.4 mg/kg) administered post-operatively for approximately 9 days (n = 101) and Group 2, meloxicam (0.3 mg/kg) administered s.c. before surgery, followed by placebo tablets administered post-operatively for approximately 9 days (n = 46). Cats were assessed using numerical rating scales (NRSs) by clinicians before surgery and at 3, 8, 22 and 28 hours after surgery and at the final visit (VF on approximately Day 10), and daily by their owners from Day 1 to the VF. The primary end point was the global investigator score which was the sum of clinician NRSs for posture, behaviour and pain on palpation/manipulation. The efficacy of the single Robenacoxib injection, assessed during 3 to 22 hours, was statistically non-inferior to meloxicam, with a relative efficacy of 1.029 (95% confidence interval, 0.847–1.231). No significant differences were detected during the follow-up treatment with Robenacoxib tablets for approximately 9 days compared with placebo via clinician assessments at 28 hours and the VF, or in owner assessments on Days 1–VF. There were no significant differences in frequencies of reported adverse events, clinical observations and haematology or clinical chemistry variables between the groups. Single s.c. injection of Robenacoxib before surgery had non-inferior efficacy compared with meloxicam in controlling post-operative pain and inflammation in cats undergoing orthopaedic surgery. Follow-up treatment with oral Robenacoxib tablets for approximately 9 days was well tolerated, but there were no differences in the efficacy scores after Day 1 compared with the group receiving meloxicam s.c. followed by placebo control.
-
Robenacoxib versus meloxicam for the management of pain and inflammation associated with soft tissue surgery in dogs a randomized non inferiority clinical trial
BMC Veterinary Research, 2013Co-Authors: Philippe Gruet, Wolfgang Seewald, J N KingAbstract:Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are used routinely to control pain and inflammation after surgery in dogs. Robenacoxib is a new NSAID with high selectivity for the cyclo-oxygenase (COX)-2 isoform of COX. The objective of this study was to evaluate the efficacy and tolerability of Robenacoxib for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs. The study was a prospective, randomized, blinded, positive-controlled, non-inferiority, multi-center clinical trial. A total of 174 dogs undergoing major soft tissue surgery were included and randomly allocated in a 2:1 ratio to receive either Robenacoxib (n = 118) or the positive control, meloxicam (n = 56). Each dog received an initial dose subcutaneously prior to surgery (Robenacoxib 2 mg/kg, meloxicam 0.2 mg/kg), followed by daily oral doses (Robenacoxib 1–2 mg/kg, meloxicam 0.1 mg/kg) for 12 days (range 10–14) after surgery. Pain and inflammation were assessed subjectively using the Glasgow Composite Pain Scale (GCPS) by clinicians as the primary end point and additional evaluations by the clinicians and animal owners as secondary endpoints. Results: Both treatments provided similar pain control, with no significant differences between groups for any efficacy variable using non-parametric analyses (Mann–Whitney U test). In no dog was analgesic rescue therapy administered. Non-inferior efficacy of Robenacoxib compared to meloxicam was demonstrated statistically for the primary and all secondary endpoints using parametric analysis of variance, although the data were not normally distributed even after log transformation. For the primary endpoint (reciprocal of the modified GCPS score), the relative efficacy of Robenacoxib/meloxicam was 1.12 with a 95% confidence interval of 0.97-1.29. Both treatments were well tolerated and did not affect buccal mucosal bleeding time. Conclusion: A treatment regimen of Robenacoxib by subcutaneous injection followed by oral tablets had good tolerability and non-inferior efficacy compared to meloxicam for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs.
Philippe Gruet - One of the best experts on this subject based on the ideXlab platform.
-
Population pharmacokinetic analysis of blood concentrations of Robenacoxib in dogs with osteoarthritis.
Research in Veterinary Science, 2013Co-Authors: Martin Fink, Ingrid M. Letellier, Mathieu Peyrou, Jonathan P. Mochel, Martin Jung, Jonathan N. King, Philippe Gruet, Jerome M. GiraudelAbstract:Abstract The purpose of this analysis was to investigate whether the recommended daily dosage of 1–2 mg/kg Robenacoxib provides consistent exposure when administered to dogs with chronic osteoarthritis (OA), and the need for dose adjustment in special patient populations. Data from three prospective, multi-center field studies in 208 OA dogs were analyzed using non-linear mixed effects modeling. A model based assessment was performed with stepwise inclusion and exclusion of population characteristics to explain between-subject variability, and assess the according necessity for dose adjustment. Only the influence of bodyweight on both apparent clearance and volume were found to be significant ( p The population pharmacokinetic analysis performed showed that the 1–2 mg/kg dosage chosen provided consistent Robenacoxib exposure in a wide range of canine patients. No other dose adjustment seems necessary.
-
Robenacoxib versus meloxicam for the management of pain and inflammation associated with soft tissue surgery in dogs a randomized non inferiority clinical trial
BMC Veterinary Research, 2013Co-Authors: Philippe Gruet, Wolfgang Seewald, J N KingAbstract:Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are used routinely to control pain and inflammation after surgery in dogs. Robenacoxib is a new NSAID with high selectivity for the cyclo-oxygenase (COX)-2 isoform of COX. The objective of this study was to evaluate the efficacy and tolerability of Robenacoxib for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs. The study was a prospective, randomized, blinded, positive-controlled, non-inferiority, multi-center clinical trial. A total of 174 dogs undergoing major soft tissue surgery were included and randomly allocated in a 2:1 ratio to receive either Robenacoxib (n = 118) or the positive control, meloxicam (n = 56). Each dog received an initial dose subcutaneously prior to surgery (Robenacoxib 2 mg/kg, meloxicam 0.2 mg/kg), followed by daily oral doses (Robenacoxib 1–2 mg/kg, meloxicam 0.1 mg/kg) for 12 days (range 10–14) after surgery. Pain and inflammation were assessed subjectively using the Glasgow Composite Pain Scale (GCPS) by clinicians as the primary end point and additional evaluations by the clinicians and animal owners as secondary endpoints. Results: Both treatments provided similar pain control, with no significant differences between groups for any efficacy variable using non-parametric analyses (Mann–Whitney U test). In no dog was analgesic rescue therapy administered. Non-inferior efficacy of Robenacoxib compared to meloxicam was demonstrated statistically for the primary and all secondary endpoints using parametric analysis of variance, although the data were not normally distributed even after log transformation. For the primary endpoint (reciprocal of the modified GCPS score), the relative efficacy of Robenacoxib/meloxicam was 1.12 with a 95% confidence interval of 0.97-1.29. Both treatments were well tolerated and did not affect buccal mucosal bleeding time. Conclusion: A treatment regimen of Robenacoxib by subcutaneous injection followed by oral tablets had good tolerability and non-inferior efficacy compared to meloxicam for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs.
-
Robenacoxib versus meloxicam for the management of pain and inflammation associated with soft tissue surgery in dogs a randomized non inferiority clinical trial
BMC Veterinary Research, 2013Co-Authors: Philippe Gruet, Wolfgang Seewald, Jonathan N. KingAbstract:Non-steroidal anti-inflammatory drugs (NSAIDs) are used routinely to control pain and inflammation after surgery in dogs. Robenacoxib is a new NSAID with high selectivity for the cyclo-oxygenase (COX)-2 isoform of COX. The objective of this study was to evaluate the efficacy and tolerability of Robenacoxib for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs. The study was a prospective, randomized, blinded, positive-controlled, non-inferiority, multi-center clinical trial. A total of 174 dogs undergoing major soft tissue surgery were included and randomly allocated in a 2:1 ratio to receive either Robenacoxib (n = 118) or the positive control, meloxicam (n = 56). Each dog received an initial dose subcutaneously prior to surgery (Robenacoxib 2 mg/kg, meloxicam 0.2 mg/kg), followed by daily oral doses (Robenacoxib 1–2 mg/kg, meloxicam 0.1 mg/kg) for 12 days (range 10–14) after surgery. Pain and inflammation were assessed subjectively using the Glasgow Composite Pain Scale (GCPS) by clinicians as the primary end point and additional evaluations by the clinicians and animal owners as secondary endpoints. Both treatments provided similar pain control, with no significant differences between groups for any efficacy variable using non-parametric analyses (Mann–Whitney U test). In no dog was analgesic rescue therapy administered. Non-inferior efficacy of Robenacoxib compared to meloxicam was demonstrated statistically for the primary and all secondary endpoints using parametric analysis of variance, although the data were not normally distributed even after log transformation. For the primary endpoint (reciprocal of the modified GCPS score), the relative efficacy of Robenacoxib/meloxicam was 1.12 with a 95% confidence interval of 0.97-1.29. Both treatments were well tolerated and did not affect buccal mucosal bleeding time. A treatment regimen of Robenacoxib by subcutaneous injection followed by oral tablets had good tolerability and non-inferior efficacy compared to meloxicam for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs.
-
Robenacoxib vs carprofen for the treatment of canine osteoarthritis a randomized noninferiority clinical trial
Journal of Veterinary Pharmacology and Therapeutics, 2012Co-Authors: Nicolas Reymond, Wolfgang Seewald, Cindy Speranza, Philippe Gruet, J N KingAbstract:Reymond, N., Speranza, C., Gruet, P., Seewald, W., King, J. N. Robenacoxib vs. carprofen for the treatment of canine osteoarthritis; a randomized, noninferiority clinical trial. J. vet. Pharmacol. Therap. 35, 175–183. Robenacoxib is a member of the coxib class of nonsteroidal anti-inflammatory drugs (NSAID), with high selectivity for the cyclooxygenase (COX)-2 isoform of COX. In this study, the efficacy and tolerability of Robenacoxib were compared with those of carprofen in canine osteoarthritis in a multi-centre, prospective, randomized, blinded, positive-controlled noninferiority clinical trial. Both drugs were administered orally once daily at recommended dosages: Robenacoxib at 1–2 mg/kg (n = 125 dogs) and racemic carprofen at 2–4 mg/kg (n = 63 dogs) for a total of 12 weeks. The efficacy of the test compounds was assessed by veterinary investigators and owners using numerical rating scales at baseline and days 7, 14, 28, 56 and 84. In both groups, all scores were significantly (P < 0.0001) improved compared with baseline at all time points (days 7–84). Robenacoxib had noninferior efficacy to carprofen for the primary endpoint, the global functional disability, both for all dogs and for the subgroup of dogs in which Robenacoxib was not administered during meals. Noninferiority was also demonstrated for three of six veterinary investigator secondary endpoints and four of six owner efficacy endpoints. For haematology and clinical chemistry variables, there were some significant differences from baseline levels but no differences between groups. There were no differences between groups in the frequencies of adverse events, which were reported in 46% dogs with Robenacoxib and 52% with carprofen (P = 0.44), which were most frequently mild events affecting the gastrointestinal tract. In conclusion, noninferior efficacy and tolerability of Robenacoxib compared with carprofen was demonstrated in dogs with osteoarthritis.
-
Robenacoxib vs carprofen for the treatment of canine osteoarthritis a randomized noninferiority clinical trial
Journal of Veterinary Pharmacology and Therapeutics, 2012Co-Authors: Nicolas Reymond, Wolfgang Seewald, Cindy Speranza, Philippe Gruet, Jonathan N. KingAbstract:Robenacoxib is a member of the coxib class of nonsteroidal anti-inflammatory drugs (NSAID), with high selectivity for the cyclooxygenase (COX)-2 isoform of COX. In this study, the efficacy and tolerability of Robenacoxib were compared with those of carprofen in canine osteoarthritis in a multi-centre, prospective, randomized, blinded, positive-controlled noninferiority clinical trial. Both drugs were administered orally once daily at recommended dosages: Robenacoxib at 1-2 mg/kg (n = 125 dogs) and racemic carprofen at 2-4 mg/kg (n = 63 dogs) for a total of 12 weeks. The efficacy of the test compounds was assessed by veterinary investigators and owners using numerical rating scales at baseline and days 7, 14, 28, 56 and 84. In both groups, all scores were significantly (P < 0.0001) improved compared with baseline at all time points (days 7-84). Robenacoxib had noninferior efficacy to carprofen for the primary endpoint, the global functional disability, both for all dogs and for the subgroup of dogs in which Robenacoxib was not administered during meals. Noninferiority was also demonstrated for three of six veterinary investigator secondary endpoints and four of six owner efficacy endpoints. For haematology and clinical chemistry variables, there were some significant differences from baseline levels but no differences between groups. There were no differences between groups in the frequencies of adverse events, which were reported in 46% dogs with Robenacoxib and 52% with carprofen (P = 0.44), which were most frequently mild events affecting the gastrointestinal tract. In conclusion, noninferior efficacy and tolerability of Robenacoxib compared with carprofen was demonstrated in dogs with osteoarthritis.
Ludovic Pelligand - One of the best experts on this subject based on the ideXlab platform.
-
Modeling of Large Pharmacokinetic Data Using Nonlinear Mixed-Effects: A Paradigm Shift in Veterinary Pharmacology. A Case Study With Robenacoxib in Cats.
CPT: pharmacometrics & systems pharmacology, 2016Co-Authors: Ludovic Pelligand, Jonathan N. King, Antoine Soubret, Jonathan Elliott, Jonathan P. MochelAbstract:The objective of this study was to model the pharmacokinetics (PKs) of Robenacoxib in cats using a nonlinear mixed-effects (NLME) approach, leveraging all available information collected from cats receiving Robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects. A bicompartmental disposition model with simultaneous zero and first-order absorption best described Robenacoxib PKs in blood. Clearance was 0.502 L/kg/h and the bioavailability was high (78%). The absorption constant point estimate (Ka = 0.68 h−1) was lower than beta (median, 1.08 h−1), unveiling flip-flop kinetics. No dosing adjustment based on available covariates information is advocated. This modeling work constitutes the first application of NLME in a large feline population.
-
Additional file 1 S1: of Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney
2015Co-Authors: Ludovic Pelligand, P. Lees, W Seewald, N. Suemanotham, J. King, H. Syme, K. Smith, J. ElliottAbstract:PK-PD integration of Robenacoxib and ketoprofen (description of data): estimation of the average duration of COX-1 and COX-2 inhibition achieved with Robenacoxib once a day (RSID), Robenacoxib twice a day (RBID) and ketoprofen (KET) using data from the literature. (DOCX 424 KB
-
differential pharmacokinetics and pharmacokinetic pharmacodynamic modelling of Robenacoxib and ketoprofen in a feline model of inflammation
Journal of Veterinary Pharmacology and Therapeutics, 2014Co-Authors: Ludovic Pelligand, J N King, J. Elliott, Pierre-louis Toutain, Victor Hormazabal, P. LeesAbstract:Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of Robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B2 concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E2 concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For Robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and Robenacoxib, respectively. Both drugs reduced exudate PGE2 concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB2 between 4 min and 24 h, whereas suppression was mild and transient with Robenacoxib. In vivoIC50COX‐1/IC50COX‐2 ratios were 66.9:1 for Robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood.
-
Differential pharmacokinetics and pharmacokinetic/pharmacodynamic modelling of Robenacoxib and ketoprofen in a feline model of inflammation
Journal of Veterinary Pharmacology and Therapeutics, 2014Co-Authors: Ludovic Pelligand, J N King, J. Elliott, Pierre-louis Toutain, Victor Hormazabal, P. LeesAbstract:Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of Robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B2 concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E2 concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For Robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and Robenacoxib, respectively. Both drugs reduced exudate PGE2 concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB2 between 4 min and 24 h, whereas suppression was mild and transient with Robenacoxib. In vivoIC50COX‐1/IC50COX‐2 ratios were 66.9:1 for Robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood.
-
pharmacokinetic pharmacodynamic modelling of Robenacoxib in a feline tissue cage model of inflammation
Journal of Veterinary Pharmacology and Therapeutics, 2012Co-Authors: Ludovic Pelligand, J N King, J. Elliott, P L Toutain, P. LeesAbstract:Pelligand, L., King, J. N., Toutain, P. L., Elliott, J., Lees, P. Pharmacokinetic/pharmacodynamic modelling of Robenacoxib in a feline tissue cage model of inflammation. J. vet. Pharmacol. Therap. 35, 19–32. Robenacoxib is a novel nonsteroidal anti-inflammatory drug developed for use in cats. It is a highly selective COX-2 inhibitor. Results from previous feline studies showed that, despite a short half-life in blood, the effect of Robenacoxib persisted for 24 h in clinical studies. A tissue cage model of acute inflammation was used to determine Robenacoxib’s pharmacokinetics and its ex vivo and in vivo selectivity for COX-1 and COX-2 using serum TxB2 and exudate PGE2 as surrogate markers for enzyme activity, respectively. After intravenous, subcutaneous and oral administration (2 mg/kg), the clearance of Robenacoxib from blood was rapid (0.54–0.71 L·h/kg). The mean residence time (MRT) in blood was short (0.4, 1.9 and 3.3 h after intravenous, subcutaneous and oral administration, respectively), but in exudate MRT was approximately 24 h regardless of the route of administration. Robenacoxib inhibition of COX-1 in blood was transient, occurring only at high concentrations, but inhibition of COX-2 in exudate persisted to 24 h. The potency ratio (IC50 COX-1: IC50 COX-2) was 171:1, and slopes of the concentration–effect relationship were 1.36 and 1.12 for COX-1 and COX-2, respectively. These data highlight the enzymatic selectivity and inflamed tissue selectivity of Robenacoxib and support the current recommendation of once-daily administration.
