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R Utzmann - One of the best experts on this subject based on the ideXlab platform.
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Meloxicam influence on arachidonic acid metabolism part ii in vivo findings
Biochemical Pharmacology, 1996Co-Authors: G Engelhardt, R Bogel, Chr Schnitzler, R UtzmannAbstract:Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Preclinical studies have indicated that Meloxicam has potent anti-inflammatory activity, together with a good gastrointestinal and renal tolerability profile. This report summarizes studies undertaken to compare Meloxicam to other NSAIDs in the inhibition of the inducible cyclooxygenase (COX-2) in inflamed areas (pleurisy of the rat, peritonitis of mice) and their influence on the activity of the constitutive cyclooxygenase (COX-1) in stomach, kidney, brain, and blood. In pleurisy of the rat, Meloxicam was twice as potent as tenoxicam, 3 times as potent as flurbiprofen, 8 times as potent as diclofenac, and 20 times as potent as tenidap at inhibiting prostaglandin E2 (PGE2) biosynthesis. In the peritonitis model in mice, Meloxicam was approximately twice as active as piroxicam, and more than 10 times as active as diclofenac in the suppression of PGE biosynthesis. Doses of Meloxicam sufficient to inhibit PGE2 biosynthesis in the pleural exudate and peritoneal exudate had no influence on leukotriene-B4 (LTB4) or leukotriene-C4 (LTC4) content. The effect of Meloxicam on the PGE2 content of rat gastric juice and rat urine was weaker than that of piroxicam or diclofenac. Meloxicam was a weaker inhibitor of the increased PGE2 concentration in brain of rats and mice (induced by convulsant doses of pentetrazole) than piroxicam, diclofenac, or indomethacin. Meloxicam had a weaker effect on serum thromboxane-B2 (TXB2) concentration in rats than piroxicam or tenoxicam. The in vivo findings confirm the results of in vitro tests, conducted separately, showing that Meloxicam preferentially inhibits COX-2 over COX-1. COX-2 is the inducible isoenzyme implicated in the inflammatory response, whereas COX-1 has cytoprotective effects in the gastric mucosa. Therefore, a preferential selectivity for one isoenzyme over another, as displayed by Meloxicam, may have implications in the clinical setting in terms of a more favorable risk: benefit profile.
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Meloxicam influence on arachidonic acid metabolism part ii in vivo findings
Biochemical Pharmacology, 1996Co-Authors: G Engelhardt, R Bogel, Chr Schnitzler, R UtzmannAbstract:Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Meloxicam has shown potent anti-inflammatory activity in animal models together with low gastrointestinal and renal toxicity. Studies were undertaken to compare Meloxicam to other NSAIDs in their ability to inhibit either constitutive cyclooxygenase (COX-1) or inducible cyclooxygenase (COX-2). COX-1 was isolated as a cell-free enzyme from bovine seminal vesicles or bovine brain or was present in nonstimulated macrophages derived from the guinea-pig peritoneum. COX-2 was induced in peritoneal macrophages stimulated by lipopolysaccharide (LPS) or isolated as a cell-free enzyme from sheep placenta. Of all NSAIDs tested, Meloxicam was the most selective inhibitor of COX-2 in intact cells. In cell-free enzyme preparations, however, Meloxicam showed the same activity against COX-1 and COX-2. All other NSAIDs tested were more potent inhibitors of COX-1 than of COX-2. The inducible cyclooxygenase COX-2 has been implicated in the mediation of the inflammatory reaction, whereas the products of the constitutive cyclooxygenase COX-1 have cytoprotective effects in the gastric mucosa, support microcirculation in the kidney, and are antithrombogenic. Therefore, differential inhibitory effects of NSAIDs on COX-1 and COX-2 may have a bearing on the risk-benefit profile displayed in clinical practice. Meloxicam shows a preferential inhibitory effect on COX-2 over COX-1, which may be directly related to the favorable tolerability profile with potent anti-inflammatory effects observed in animal studies.
Takanori Hattori - One of the best experts on this subject based on the ideXlab platform.
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a selective cyclooxygenase 2 inhibitor prevents inflammation related squamous cell carcinogenesis of the forestomach via duodenogastric reflux in rats
Cancer, 2009Co-Authors: Masaru Oba, Koichi Miwa, Takashi Fujimura, Shinichi Harada, Shozo Sasaki, Katsunobu Oyama, Tetsuo Ohta, Takanori HattoriAbstract:BACKGROUND: Duodenal reflux causes inflammation-related squamous cell carcinogenesis in the forestomach of rats without any carcinogens. The aim of this study was to investigate the efficacy of a selective cyclooxygenase (COX)-2 inhibitor, Meloxicam, in preventing this carcinogenesis. METHODS: A series of 188 rats underwent a surgical duodenogastric reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other was given experimental chow containing Meloxicam (0.3 mg/kg body weight/day) (Meloxicam group). The animals were sequentially sacrificed at Weeks 20, 30, 40, 50, and 60 after surgery. The forestomach was examined for the presence of carcinoma, the incidence of reflux-related morphological changes, COX-2 expression, and its activity. RESULTS: At Week 60, squamous cell carcinoma developed in 8 of 21 animals (38%) in the control group, but none of 20 (0%) in the Meloxicam group (P < .05). In addition, basal cell dysplasia developed in 19 of 21 (90%) animals in the control group, but only 4 of 20 (20%) in the Meloxicam group (P < .01). COX-2 immunoreactivity was predominantly detected in macrophages in the epithelial stroma. Compared with nonsurgical rats, RNA expression of COX-2 in the epithelium was up-regulated, reaching peak at an early stage of Week 20 in both groups (P < .005). The expression of microsomal prostaglandin E synthase-1 was lower in the Meloxicam group than in the control group. PGE2 production was significantly suppressed throughout the experiment in the Meloxicam group compared with the control group (P < .005). CONCLUSIONS: Meloxicam was effective in preventing reflux-induced squamous cell carcinogenesis via an inflamed squamous epithelium. Cancer 2009. © 2009 American Cancer Society.
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a selective cyclooxygenase 2 inhibitor prevents inflammation related squamous cell carcinogenesis of the forestomach via duodenogastric reflux in rats
Cancer, 2009Co-Authors: Koichi Miwa, Takashi Fujimura, Shinichi Harada, Shozo Sasaki, Katsunobu Oyama, Tetsuo Ohta, Takanori HattoriAbstract:BACKGROUND: Duodenal reflux causes inflammation-related squamous cell carcinogenesis in the forestomach of rats without any carcinogens. The aim of this study was to investigate the efficacy of a selective cyclooxygenase (COX)-2 inhibitor, Meloxicam, in preventing this carcinogenesis. METHODS: A series of 188 rats underwent a surgical duodenogastric reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other was given experimental chow containing Meloxicam (0.3 mg/kg body weight/day) (Meloxicam group). The animals were sequentially sacrificed at Weeks 20, 30, 40, 50, and 60 after surgery. The forestomach was examined for the presence of carcinoma, the incidence of reflux-related morphological changes, COX-2 expression, and its activity. RESULTS: At Week 60, squamous cell carcinoma developed in 8 of 21 animals (38%) in the control group, but none of 20 (0%) in the Meloxicam group (P < .05). In addition, basal cell dysplasia developed in 19 of 21 (90%) animals in the control group, but only 4 of 20 (20%) in the Meloxicam group (P < .01). COX-2 immunoreactivity was predominantly detected in macrophages in the epithelial stroma. Compared with nonsurgical rats, RNA expression of COX-2 in the epithelium was up-regulated, reaching peak at an early stage of Week 20 in both groups (P < .005). The expression of microsomal prostaglandin E synthase-1 was lower in the Meloxicam group than in the control group. PGE2 production was significantly suppressed throughout the experiment in the Meloxicam group compared with the control group (P < .005). CONCLUSIONS: Meloxicam was effective in preventing reflux-induced squamous cell carcinogenesis via an inflamed squamous epithelium. Cancer 2009. © 2009 American Cancer Society.
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chemoprevention of glandular stomach carcinogenesis through duodenogastric reflux in rats by a cox 2 inhibitor
International Journal of Cancer, 2008Co-Authors: Koichi Miwa, Takashi Fujimura, Shinichi Harada, Shozo Sasaki, Takanori HattoriAbstract:Duodenogastric reflux (DGR) causes glandular stomach carcinogenesis in rats without carcinogens. We aimed to investigate how this carcinogenesis might be prevented by a selective COX-2 inhibitor, Meloxicam. A series of 188 Fisher 344 rats underwent a surgical DGR procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other an experimental chow containing Meloxicam [0.3 mg/kg bw/day] (Meloxicam group). The animals were sequentially sacrificed at weeks 20, 30, 40, 50 and 60 after surgery. The stomachs were removed and examined for the presence of carcinoma, incidence of reflux-induced morphologic changes, COX-2 expression and its activity. Adenocarcinoma in the glandular stomach developed in 7 of 21 animals (33%) in the control group at week 60, but none of 20 (0%) in the Meloxicam group (p < 0.01). Moreover, reflux-induced gastritis was definitely alleviated in the Meloxicam group compared with the control group. COX-2 immunoreactivity was predominantly detected in stromal cells such as macrophages and fibroblasts. Compared with nonsurgical rats, RNA expression of COX-2 in the mucosa increased, reaching peak at an early phase of week 20 in both groups (p < 0.005). Expression of microsomal prostaglandin E synthase-1 was lower in the Meloxicam group than in the control group. PGE2 production was significantly suppressed throughout the experiment in the Meloxicam group compared with the control group (p < 0.01). Gastric carcinogenesis via duodenal reflux was mediated by the COX-2 pathway in rats. Administration of Meloxicam prevented this carcinogenesis by suppressing the inflammatory process. © 2008 Wiley-Liss, Inc.
G Engelhardt - One of the best experts on this subject based on the ideXlab platform.
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Meloxicam influence on arachidonic acid metabolism part ii in vivo findings
Biochemical Pharmacology, 1996Co-Authors: G Engelhardt, R Bogel, Chr Schnitzler, R UtzmannAbstract:Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Preclinical studies have indicated that Meloxicam has potent anti-inflammatory activity, together with a good gastrointestinal and renal tolerability profile. This report summarizes studies undertaken to compare Meloxicam to other NSAIDs in the inhibition of the inducible cyclooxygenase (COX-2) in inflamed areas (pleurisy of the rat, peritonitis of mice) and their influence on the activity of the constitutive cyclooxygenase (COX-1) in stomach, kidney, brain, and blood. In pleurisy of the rat, Meloxicam was twice as potent as tenoxicam, 3 times as potent as flurbiprofen, 8 times as potent as diclofenac, and 20 times as potent as tenidap at inhibiting prostaglandin E2 (PGE2) biosynthesis. In the peritonitis model in mice, Meloxicam was approximately twice as active as piroxicam, and more than 10 times as active as diclofenac in the suppression of PGE biosynthesis. Doses of Meloxicam sufficient to inhibit PGE2 biosynthesis in the pleural exudate and peritoneal exudate had no influence on leukotriene-B4 (LTB4) or leukotriene-C4 (LTC4) content. The effect of Meloxicam on the PGE2 content of rat gastric juice and rat urine was weaker than that of piroxicam or diclofenac. Meloxicam was a weaker inhibitor of the increased PGE2 concentration in brain of rats and mice (induced by convulsant doses of pentetrazole) than piroxicam, diclofenac, or indomethacin. Meloxicam had a weaker effect on serum thromboxane-B2 (TXB2) concentration in rats than piroxicam or tenoxicam. The in vivo findings confirm the results of in vitro tests, conducted separately, showing that Meloxicam preferentially inhibits COX-2 over COX-1. COX-2 is the inducible isoenzyme implicated in the inflammatory response, whereas COX-1 has cytoprotective effects in the gastric mucosa. Therefore, a preferential selectivity for one isoenzyme over another, as displayed by Meloxicam, may have implications in the clinical setting in terms of a more favorable risk: benefit profile.
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Meloxicam influence on arachidonic acid metabolism part ii in vivo findings
Biochemical Pharmacology, 1996Co-Authors: G Engelhardt, R Bogel, Chr Schnitzler, R UtzmannAbstract:Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Meloxicam has shown potent anti-inflammatory activity in animal models together with low gastrointestinal and renal toxicity. Studies were undertaken to compare Meloxicam to other NSAIDs in their ability to inhibit either constitutive cyclooxygenase (COX-1) or inducible cyclooxygenase (COX-2). COX-1 was isolated as a cell-free enzyme from bovine seminal vesicles or bovine brain or was present in nonstimulated macrophages derived from the guinea-pig peritoneum. COX-2 was induced in peritoneal macrophages stimulated by lipopolysaccharide (LPS) or isolated as a cell-free enzyme from sheep placenta. Of all NSAIDs tested, Meloxicam was the most selective inhibitor of COX-2 in intact cells. In cell-free enzyme preparations, however, Meloxicam showed the same activity against COX-1 and COX-2. All other NSAIDs tested were more potent inhibitors of COX-1 than of COX-2. The inducible cyclooxygenase COX-2 has been implicated in the mediation of the inflammatory reaction, whereas the products of the constitutive cyclooxygenase COX-1 have cytoprotective effects in the gastric mucosa, support microcirculation in the kidney, and are antithrombogenic. Therefore, differential inhibitory effects of NSAIDs on COX-1 and COX-2 may have a bearing on the risk-benefit profile displayed in clinical practice. Meloxicam shows a preferential inhibitory effect on COX-2 over COX-1, which may be directly related to the favorable tolerability profile with potent anti-inflammatory effects observed in animal studies.
Butch Kukanich - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics of single dose subcutaneous Meloxicam injections in black tailed prairie dogs cynomys ludovicianus
Journal of The American Association for Laboratory Animal Science, 2017Co-Authors: Thomas L Wright, David Eshar, Christina Mccullough, Matt Warner, Butch KukanichAbstract:This study evaluated the pharmacokinetic profile of a single dose of Meloxicam (1.0 mg/kg) administered subcutaneously (n = 6) or intravenously (n = 2) to black-tailed prairie dogs (Cynomys ludovicianus). Blood was collected immediately before (time 0) and at 0.5, 1, 2, 4, 8, 12 and 24 h after drug administration. Plasma Meloxicam concentrations were quantified with HPLC-mass spectrometry, and noncompartmental pharmacokinetic analysis was performed. The peak plasma concentrations, time to peak plasma concentration, and terminal half-life of Meloxicam after subcutaneous administration (median [minimum-maximum]) were 4.30 (3.00-4.89) μg/mL, 2.00 (0.62-4.00) h, and 11.88 (7.35-18.64) h, respectively. Plasma concentrations of Meloxicam for prairie dogs in the present study showed high absorption and slow elimination after drug administration. The results of this study suggest that a 1.0-mg/kg SC dose of Meloxicam administered every 24 h might be excessive for prairie dogs, although the ideal therapeutic dose in terms of safety and efficacy is unknown in this species.
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pharmacokinetics of Meloxicam administered orally to rabbits oryctolagus cuniculus for 29 days
American Journal of Veterinary Research, 2014Co-Authors: Katie W Delk, Butch Kukanich, J W Carpenter, Jerome C Nietfeld, Micah KohlesAbstract:Objective—To determine the pharmacokinetics and safety of Meloxicam in rabbits when administered orally for 29 days. Animals—6 healthy rabbits. Procedures—Meloxicam (1.0 mg/kg, PO, q 24 h) was administered to rabbits for 29 days. Blood was collected immediately before (time 0) and 2, 4, 6, 8, and 24 hours after drug administration on days 1, 8, 15, 22, and 29 to evaluate the pharmacokinetics of Meloxicam. On day 30, an additional sample was collected 36 hours after treatment. Plasma Meloxicam concentrations were quantified with liquid chromatography–mass spectrometry, and noncompartmental pharmacokinetic analysis was performed. Weekly plasma biochemical analyses were performed to evaluate any adverse physiologic effects. Rabbits were euthanatized for necropsy on day 31. Results—Mean ± SD peak plasma concentrations of Meloxicam after administration of doses 1, 8, 15, 22, and 29 were 0.67 ± 0.19 μg/mL, 0.81 ± 0.21 μg/mL, 1.00 ± 0.31 μg/mL, 1.00 ± 0.29 μg/mL, and 1.07 ± 0.19 μg/mL, respectively; these concen...
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the effect of timing of oral Meloxicam administration on physiological responses in calves after cautery dehorning with local anesthesia
Journal of Dairy Science, 2013Co-Authors: K A Allen, Johann F Coetzee, L N Edwardscallaway, H Glynn, J C Dockweiler, Butch Kukanich, Hui Lin, Chunkao Wang, E Fraccaro, M JonesAbstract:Abstract Dehorning is a painful husbandry procedure that is commonly performed in dairy calves. Parenteral Meloxicam combined with local anesthesia mitigates the physiological and behavioral effects of dehorning in calves. The purpose of this study was to determine the influence of timing of oral Meloxicam administration on physiological responses in calves after dehorning. Thirty Holstein bull calves, 8 to 10 wk of age (28–70kg), were randomly assigned to 1 of 3 treatment groups: placebo-treated control group (n=10), calves receiving Meloxicam administered orally (1 mg/kg) in powdered milk replacer 12h before cautery dehorning (MEL-PRE; n=10), and calves receiving Meloxicam administered as an oral bolus (1 mg/kg) at the time of dehorning (MEL-POST; n=10). Following cautery dehorning, blood samples were collected to measure cortisol, substance P (SP), haptoglobin, ex vivo prostaglandin E 2 (PgE 2 ) production after lipopolysaccharide stimulation and Meloxicam concentrations. Maximum ocular temperature and mechanical nociceptive threshold (MNT) were also assessed. Data were analyzed using noncompartmental pharmacokinetic analysis and repeated measures ANOVA models. Mean peak Meloxicam concentrations were 3.61±0 0.21 and 3.27±0.14μg/mL with average elimination half-lives of 38.62±5.87 and 35.81±6.26h for MEL-PRE and MEL-POST, respectively. Serum cortisol concentrations were lower in Meloxicam-treated calves compared with control calves at 4h postdehorning. Substance P concentrations were significantly higher in control calves compared with Meloxicam-treated calves at 120h after dehorning. Prostaglandin E 2 concentrations were lower in Meloxicam-treated calves compared with control calves. Mechanical nociceptive threshold was higher in control calves at 1h after dehorning, but Meloxicam-treated calves tended to have a higher MNT at 6h after dehorning. No effect of timing of Meloxicam administration on serum cortisol concentrations, SP concentrations, haptoglobin concentrations, maximum ocular temperature, or MNT was observed. However, PgE 2 concentrations in MEL-PRE calves were similar to control calves after 12h postdehorning, whereas MEL-POST calves had lower PgE 2 concentrations for 3 d postdehorning. These findings support that Meloxicam reduced cortisol, SP, and PgE 2 after dehorning, but only PgE 2 production was significantly affected by the timing of Meloxicam administration.
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a study to compare circulating flunixin Meloxicam and gabapentin concentrations with prostaglandin e2 levels in calves undergoing dehorning
Research in Veterinary Science, 2013Co-Authors: E Fraccaro, Johann F Coetzee, L N Edwardscallaway, H Glynn, Butch Kukanich, R Odore, P Badino, Luigi Bertolotti, J Dockweiler, K AllenAbstract:Abstract The purpose of this study was to investigate the pharmacokinetics of intravenous flunixin (2.2 mg/kg b.w.), oral Meloxicam (1 mg/kg b.w.), oral gabapentin (15 mg/kg b.w.) alone or co-administrated with Meloxicam as well as the effects of these compounds on prostaglandin E2 (PGE2) synthesis in calves subjected to surgical dehorning. Plasma samples collected up to 24 h after drug administration were analyzed by liquid chromatography/mass spectrometry, whereas blood PGE2 levels were measured by immunoenzymatic assay. In plasma, the terminal half-live of flunixin, Meloxicam and gabapentin were 6.0 h (range, 3.4–11.0 h), 16.7 h (range, 13.7–21.3 h) and 15.3 h (range, 11–32.9 h), respectively. The co-administration of single doses of gabapentin and Meloxicam did not seem to affect the pharmacokinetic profile of the two drugs except for gabapentin that reached significantly (P
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pharmacokinetics of Meloxicam in rabbits after oral administration of single and multiple doses
American Journal of Veterinary Research, 2013Co-Authors: Daniel V Fredholm, Butch Kukanich, J W Carpenter, Micah KohlesAbstract:Objective—To determine the pharmacokinetics of Meloxicam (1 mg/kg) in rabbits after oral administration of single and multiple doses. Animals—6 healthy rabbits. Procedures—A single dose of Meloxicam (1 mg/kg, PO) was administered to the rabbits. After a 10-day washout period, Meloxicam (1 mg/kg, PO) was administered to rabbits every 24 hours for 5 days. Blood samples were obtained from rabbits at predetermined intervals during both treatment periods. Plasma Meloxicam concentrations were determined, and noncompartmental pharmacokinetic analysis was performed. Results—The mean peak plasma concentration and area under the plasma concentration-versus-time curve extrapolated to infinity after administration of a single dose of Meloxicam were 0.83 μg/mL and 10.37 h•μg/mL, respectively. After administration of Meloxicam for 5 days, the mean peak plasma concentration was 1.33 μg/mL, and the area under the plasma concentration-versus-time curve from the time of administration of the last dose to 24 hours after tha...
Johann F Coetzee - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics of oral and subcutaneous Meloxicam: Effect on indicators of pain and inflammation after knife castration in weaned beef calves
2019Co-Authors: Daniela M. Meléndez, Johann F Coetzee, Sonia Marti, Edmond A. Pajor, Pritam K. Sidhu, Désirée Gellatly, Eugene D. Janzen, Timothy D. Schwinghamer, Karen S. Schwartzkopf-gensweinAbstract:Oral Meloxicam is labelled for reducing pain and inflammation associated with castration in cattle in Canada, however, subcutaneous Meloxicam is only labelled for pain associated with dis-budding and abdominal surgery. The aim of this project was to determine the pharmacokinetic profile of oral (PO; 1.0 mg/kg BW) and subcutaneous Meloxicam (SC; 0.5 mg/kg BW), and to assess the effect of Meloxicam on physiological and behavioural indicators of pain associated with knife castration in 7–8 month old calves. Twenty-three Angus crossbred beef calves (328 ± 4.4 kg BW) were randomly assigned to two treatments: PO n = 12 or SC n = 11 administration of Meloxicam immediately before knife castration. Physiological parameters included salivary and hair cortisol, substance P, haptoglobin, serum amyloid-A, weight, complete blood count, scrotal and rectal temperature. Behavioural parameters included standing and lying behaviour, pen behaviour and feeding behaviour. Data were analyzed using PROC GLIMMIX (SAS), with repeated measures using mixed procedures including treatment as a fixed effect and animal and pen as a random effect. The pharmacokinetic profile of the drug including area under the curve, volume of distribution and clearance was greater (P
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the effect of timing of oral Meloxicam administration on physiological responses in calves after cautery dehorning with local anesthesia
Journal of Dairy Science, 2013Co-Authors: K A Allen, Johann F Coetzee, L N Edwardscallaway, H Glynn, J C Dockweiler, Butch Kukanich, Hui Lin, Chunkao Wang, E Fraccaro, M JonesAbstract:Abstract Dehorning is a painful husbandry procedure that is commonly performed in dairy calves. Parenteral Meloxicam combined with local anesthesia mitigates the physiological and behavioral effects of dehorning in calves. The purpose of this study was to determine the influence of timing of oral Meloxicam administration on physiological responses in calves after dehorning. Thirty Holstein bull calves, 8 to 10 wk of age (28–70kg), were randomly assigned to 1 of 3 treatment groups: placebo-treated control group (n=10), calves receiving Meloxicam administered orally (1 mg/kg) in powdered milk replacer 12h before cautery dehorning (MEL-PRE; n=10), and calves receiving Meloxicam administered as an oral bolus (1 mg/kg) at the time of dehorning (MEL-POST; n=10). Following cautery dehorning, blood samples were collected to measure cortisol, substance P (SP), haptoglobin, ex vivo prostaglandin E 2 (PgE 2 ) production after lipopolysaccharide stimulation and Meloxicam concentrations. Maximum ocular temperature and mechanical nociceptive threshold (MNT) were also assessed. Data were analyzed using noncompartmental pharmacokinetic analysis and repeated measures ANOVA models. Mean peak Meloxicam concentrations were 3.61±0 0.21 and 3.27±0.14μg/mL with average elimination half-lives of 38.62±5.87 and 35.81±6.26h for MEL-PRE and MEL-POST, respectively. Serum cortisol concentrations were lower in Meloxicam-treated calves compared with control calves at 4h postdehorning. Substance P concentrations were significantly higher in control calves compared with Meloxicam-treated calves at 120h after dehorning. Prostaglandin E 2 concentrations were lower in Meloxicam-treated calves compared with control calves. Mechanical nociceptive threshold was higher in control calves at 1h after dehorning, but Meloxicam-treated calves tended to have a higher MNT at 6h after dehorning. No effect of timing of Meloxicam administration on serum cortisol concentrations, SP concentrations, haptoglobin concentrations, maximum ocular temperature, or MNT was observed. However, PgE 2 concentrations in MEL-PRE calves were similar to control calves after 12h postdehorning, whereas MEL-POST calves had lower PgE 2 concentrations for 3 d postdehorning. These findings support that Meloxicam reduced cortisol, SP, and PgE 2 after dehorning, but only PgE 2 production was significantly affected by the timing of Meloxicam administration.
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a study to compare circulating flunixin Meloxicam and gabapentin concentrations with prostaglandin e2 levels in calves undergoing dehorning
Research in Veterinary Science, 2013Co-Authors: E Fraccaro, Johann F Coetzee, L N Edwardscallaway, H Glynn, Butch Kukanich, R Odore, P Badino, Luigi Bertolotti, J Dockweiler, K AllenAbstract:Abstract The purpose of this study was to investigate the pharmacokinetics of intravenous flunixin (2.2 mg/kg b.w.), oral Meloxicam (1 mg/kg b.w.), oral gabapentin (15 mg/kg b.w.) alone or co-administrated with Meloxicam as well as the effects of these compounds on prostaglandin E2 (PGE2) synthesis in calves subjected to surgical dehorning. Plasma samples collected up to 24 h after drug administration were analyzed by liquid chromatography/mass spectrometry, whereas blood PGE2 levels were measured by immunoenzymatic assay. In plasma, the terminal half-live of flunixin, Meloxicam and gabapentin were 6.0 h (range, 3.4–11.0 h), 16.7 h (range, 13.7–21.3 h) and 15.3 h (range, 11–32.9 h), respectively. The co-administration of single doses of gabapentin and Meloxicam did not seem to affect the pharmacokinetic profile of the two drugs except for gabapentin that reached significantly (P
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pharmacokinetics and effect of intravenous Meloxicam in weaned holstein calves following scoop dehorning without local anesthesia
BMC Veterinary Research, 2012Co-Authors: Johann F Coetzee, Butch Kukanich, R A Mosher, Ronette Gehring, Brad Robert, Brandon J Reinbold, B J WhiteAbstract:Dehorning is a common practice involving calves on dairy operations in the United States. However, less than 20% of producers report using analgesics or anesthetics during dehorning. Administration of a systemic analgesic drug at the time of dehorning may be attractive to dairy producers since cornual nerve blocks require 10 – 15 min to take effect and only provide pain relief for a few hours. The primary objectives of this trial were to (1) describe the compartmental pharmacokinetics of Meloxicam in calves after IV administration at 0.5 mg/kg and (2) to determine the effect of Meloxicam (n = 6) or placebo (n = 6) treatment on serum cortisol response, plasma substance P (SP) concentrations, heart rate (HR), activity and weight gain in calves after scoop dehorning and thermocautery without local anesthesia. Plasma Meloxicam concentrations were detectable for 50 h post-administration and fit a 2-compartment model with a rapid distribution phase (mean T½α = 0.22 ± 0.087 h) and a slower elimination phase (mean T½β = 21.86 ± 3.03 h). Dehorning caused a significant increase in serum cortisol concentrations and HR (P < 0.05). HR was significantly lower in the Meloxicam-treated calves compared with placebo-treated calves at 8 h (P = 0.039) and 10 h (P = 0.044) after dehorning. Mean plasma SP concentrations were lower in Meloxicam treated calves (71.36 ± 20.84 pg/mL) compared with control calves (114.70 ± 20.84 pg/mL) (P = 0.038). Furthermore, the change in plasma SP from baseline was inversely proportional to corresponding plasma Meloxicam concentrations (P = 0.008). The effect of dehorning on lying behavior was less significant in Meloxicam-treated calves (p = 0.40) compared to the placebo-treated calves (P < 0.01). Calves receiving Meloxicam prior to dehorning gained on average 1.05 ± 0.13 kg bodyweight/day over 10 days post-dehorning compared with 0.40 ± 0.25 kg bodyweight/day in the placebo-treated calves (p = 0.042). To our knowledge, this is the first published report examining the effects of Meloxicam without local anesthesia on SP, activity and performance of calves post-dehorning. These findings suggest that administration of Meloxicam alone immediately prior to dehorning does not mitigate signs of acute distress but may have long term physiological, behavior and performance effects.
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bioavailability and pharmacokinetics of oral Meloxicam in llamas
BMC Veterinary Research, 2012Co-Authors: Amanda J Kreuder, Johann F Coetzee, Butch Kukanich, Larry W Wulf, Jennifer A Schleining, Lori L Layman, Paul J PlummerAbstract:South American camelids in the United States have rapidly developed into an important agricultural industry in need of veterinary services. Pain management is challenging in camelids because there are no drugs currently approved by the U.S. Food and Drug Administration for use in these species. Dosage regimens used for many therapeutic drugs have been extrapolated from other ruminants; however, the pharmacokinetics, in camelids, may differ from those of other species. Studies investigating the pharmacokinetics of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs in camelids are deficient in the published literature. Six adult llamas (121- 168 kg) were administered either a 1 mg/kg dose of oral or a 0.5 mg/kg dose of IV Meloxicam in a randomized cross-over design with an 11 day washout period between treatments. Plasma samples collected up to 96 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry detection (HPLC-MS) followed by non-compartmental pharmacokinetic analysis. A mean peak plasma concentration (CMAX) of 1.314 μg/mL (Range: 0.826 – 1.776 μg/mL) was recorded at 21.4 hours (Range: 12.0 – 24.0 hours) with a half-life (T ½ λz) of 22.7 hours (Range: 18.0 – 30.8 hours) after oral Meloxicam administration. In comparison, a half-life (T ½ λz) of 17.4 hours (Range: 16.2 – 20.7 hours) was demonstrated with IV Meloxicam administration. The oral bioavailability (F) of Meloxicam (dose normalized) was 76% (Range: 48 – 92%). No adverse effects associated with either treatment modality were observed in the llamas. The mean bioavailability (F) of oral Meloxicam was 76% indicating a high degree of gastrointestinal absorption. Plasma Meloxicam concentrations >0.2 μg/mL were maintained for up to 72 h after oral administration; >0.2 μg/mL is considered to be the concentration of Meloxicam required for analgesic effects in other species such as the horse. These data suggest that a single dosage of oral Meloxicam at 1 mg/kg could potentially maintain therapeutic concentrations in plasma for up to 3 days in adult llamas.