Dose Of Meloxicam Research Articles

Determining the Pharmacokinetic Properties of Two Different Doses of Meloxicam in Barred Owls (Strix varia)

Anthropogenic activities have negatively affected many birds, including owls. The Wildlife Hospital of Louisiana (WHL) has seen a 3.2-fold increase in barred owl (Strix varia) cases over the past eight years (2023, 134; 2015, 42). Because most of these animals present with traumatic injuries, analgesics should be considered in their treatment plan. To date, no study has measured the pharmacokinetics of an analgesic in barred owls. The goals of this study were to determine the harmonic means, times to maximum concentration, and elimination half-lives for single 1 mg/kg and 2 mg/kg intramuscular doses of meloxicam. Twelve barred owls (1 mg/kg, n = 6; 2 mg/kg, n = 6) admitted to the WHL and determined to be clinically normal based on examination and blood work were recruited for this study. Meloxicam was administered intramuscularly, and blood samples were collected intermittently over 12 h to measure plasma concentrations using high-performance liquid chromatography. Both doses had rapid elimination half-lives (1 mg/kg, 0.99 ± 0.1 h; 2 mg/kg, 1.07 ± 0.43 h) and were below the limits of quantification (0.1 µg/mL) by 6–12 h. Based on these results, 1 and 2 mg/kg doses of meloxicam were found to produce plasma concentrations below therapeutic concentrations for less than four hours, making current twice-daily recommended dosing intervals unlikely to provide desired analgesia.

Comparative pharmacokinetics of a single oral dose of meloxicam in the California sea lion (Zalophus californianus) and Pacific harbor seal (Phoca vitulina richardii).

Pharmacokinetics studies have investigated meloxicam, a non-steroidal anti-inflammatory drug, dosing strategies in a wide variety of non-domestic animals; however, there is no prior study examining well-founded dosing for pinnipeds. To develop dosing protocols, pharmacokinetic information is needed, with an examination of differences between pinniped species. Apparently, healthy California sea lions (Zalophus californianus: CSL; n = 13) and Pacific harbor seals (Phoca vitulina richardii: PHS; n = 17) that had completed rehabilitation were enrolled into a population-based pharmacokinetic study. Each animal was administered a single oral dose of meloxicam at 0.1 mg/kg, and two blood samples were collected from each animal at varying intervals during a 96-h study period. Plasma concentrations of meloxicam were determined by high-pressure liquid chromatography. Data were analyzed with nonlinear mixed effects modeling (Phoenix® NLME™, Certara, St. Louis, MO 63105, USA). The results indicated that in PHS, peak plasma concentration (Cmax) was 0.33 μg/mL with an elimination half-life (Ke t½) of 31.53 h. In CSL, Cmax was 0.17 μg/mL with Ke t½ of 32.71 h. All animals enrolled completed the study without outward adverse clinical signs. The elimination half-life was longer than previously recommended dosing intervals for pinnipeds; however, we cannot speculate in the optimum clinical dose from these results.

PSII-2 Evaluation of Meloxicam in Sows Post-Farrowing on Sow and Piglet Performance

Abstract Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) often used in humans and companion animals to treat arthritis, having strong anti-inflammatory and fever-reducing properties. The objectives of this study were to evaluate the effects of a new compounded oral drench suspension formulation of Meloxicam on sow body temperature in the first 24 hours after farrowing, piglet survivability, and piglet growth. A total of 851 sows in a commercial farm were randomly assigned to receive a single, 90 mg dose (6 mL of a 1.5% suspension) of Meloxicam via oral drench at completion of farrowing (MEL, n = 428) or receive no drug after farrowing (CON, n = 423). Rectal temperatures were taken at the end of farrowing, and 12 and 24 hours after farrowing to monitor sow body temperatures. As standard practice on this farm, sows with a temperature ≥ 39.7 °C at 24 hours post-farrowing were treated with flunixin (NSAID) and ampicillin injectables for 3 consecutive days (MEDS). Litter size and weights were recorded on day 0 and again on the day before weaning. Piglet deaths and reasons were recorded daily to determine piglet survivability and the body weights of dead piglets were recorded. The Mixed procedure of SAS 9.4 (Cary, North Carolina) was used to analyze the interaction between treatment (MEL or CON) and parity (P1 vs. P2 and P3 vs. P>3) as the main effects. A 2x2 factorial design was used to reanalyze the interaction of Meloxicam treatment with additional medicated pigs (MEDS) using PROC Mixed in SAS with MEL and MEDS as main effects, and litter birthweight quartile and number nursed covariates where appropriate. MEL was successful in reducing the temperature of sows by 0.16 °C in the first 12 hours after farrowing (P = 0.0013). For all groups, sows greater than parity 3 had lower temperatures in the first 24 hours after farrowing (P = 0.0083). Gilts in the MEL group required less additional medication than gilts in the CON group (P = 0.0102). Treating sows with Meloxicam tended to reduce the incidence of scours in piglets (P = 0.0907). MEL did not significantly (P > 0.05) impact preweaning mortality (CON = 12.9%, MEL = 12.3%), piglet weaning weight (CON: 5.4 kg ± 0.10; MEL: 5.5 kg ± 0.04), and no differences were observed between piglet weight and age at death between the treatment groups. This study exhibits the ability of a single dose of Meloxicam at farrowing to reduce fever within the first 12 hours of dosing and its potential to reduce the incidence of scours in piglets. Future studies investigating a longer Meloxicam therapy period post-farrowing will give insight into the use of Meloxicam as a fever-reducer to improve sow and piglet lactation performance and survivability.

Seasonal distribution of repeat breeder cows and evaluation of modified protocols for post AI treatment during summer.

An important problem of dairy industry worldwide is repeat breeder cows (RB). In this study, one farm in Northern Greece was chosen on the basis of subfertility. First, the available reproductive data of the previous year were evaluated; then, the farmer was advised to use the most common treatments for RB [GnRH with the third artificial insemination (AI+GnRH) or ovsynch in cows found empty after the second AI], and their efficacy was monitored throughout the year. Cows (n = 147) 2.5 to 4.5 years old were included. During the next year, post AI treatments (meta-ovsynch and meta-AI) were used during summer; GnRH (100 μg of gonadorelin) alone or in combination with meloxicam (0.5 mg/kg BW) was used during summer. Meta-ovsynch protocols were administered to 29 cows detected as non-pregnant after 3 AIs; cows were divided randomly into 3 meta-ovsynch (OS) groups: group OS (controls, n = 10), standard ovsynch protocol; group OS+GnRH (n = 10), OS plus GnRH 10 days after AI; and group OS+GnRH+NSAID (n = 9), OS plus GnRH 10 days after AI plus meloxicam 15 days after AI. Meta-AI protocols were tested in 27 RB cows; cows were divided randomly into 3 AI groups: GnRH (n = 9), 1 dose of GnRH with AI; GnRH-GnRH (n = 9), two doses of GnRH, one with AI and another 10 days later; and GnRH-GnRH-NSAID (n = 9), two doses of GnRH as in GnRH-GnRH group and one dose of meloxicam 15 days after AI. Pregnancy diagnosis was performed by ultrasound 38 days after AI. During the 1st year of evaluation, 53.79% of cows had received ≥ 3 AIs; the highest percentage (38.48%) of RB cows was recorded during autumn. After treatment for RB, the lowest (P < 0.05) pregnancy rate (PR) was recorded in August (18.18%) compared to January (75.0%), May (53.33%), and December (50.0%, P < 0.1). The efficacy of ovsynch during winter was significantly higher compared to all the other seasons. The percentage of cows with increased estrous cycle duration (24-37 days) after RB treatment and AI was the highest (P < 0.05) in spring and summer after AI+GnRH and the lowest (P < 0.05) during winter after ovsynch. Concerning the post AI treatments during summer, significantly higher pregnancy rate was recorded in the OS+GnRH+NSAID group (55.55%) compared to OS+GnRH (10%) and OS (10%) groups. Pregnancy rates did not differ among AI groups. It seems that OS+GnRH+NSAID is a promising protocol for RB cows during summer although further research is needed to support the present results.

Milk residues following multiple doses of meloxicam and gabapentin in lactating dairy cattle.

To determine the influence of stage of lactation on the pharmacokinetics in milk when multiple doses of meloxicam were administered alone or in combination with gabapentin to postpartum (PP) and mid-lactation (ML) cows. 8 postpartum and 8 mid-lactation dairy cows. Cows were randomly divided into 2 groups (n = 8) which included 4 PP cows and 4 ML cows. Group I received only 6 oral daily doses of meloxicam (1.0 mg/kg for 6 doses). Group II received 6 oral daily doses of co-administered meloxicam (1.0 mg/kg) and gabapentin (20 mg/kg) for 6 doses. Meloxicam and gabapentin were quantified in plasma and milk samples by ultra-high-performance liquid chromatography-tandem mass spectrometry, and the pharmacokinetic analysis of milk and plasma was performed using a non-compartmental approach. Regardless of lactation status, dairy cattle administered multiple doses of meloxicam and/or gabapentin showed low drug residue concentrations and little accumulation in milk. The terminal plasma half-life of meloxicam was significantly increased (P < .02) in PP cows (12.9 hr) compared to ML cows (9.4 hr). The apparent terminal half-life in milk for meloxicam and gabapentin was not affected by stage of lactation. Co-administration of gabapentin did not alter plasma or milk concentrations of meloxicam. The results of this study suggest that milk from cows treated with multiple doses of meloxicam alone or in combination with gabapentin will have low drug concentrations and falls below our reported limit of detection for meloxicam or gabapentin 120 and 60 hours respectively, following the final dose regardless of their stage of lactation.

Toxicological effects of meloxicam on physiological and antioxidant status of common carp (Cyprinus carpio).

Fish in aquatic environments are end consumers of the food chain and are widely used for the evolution effects of environmental pollution and their interactions in aquatic ecosystem. In the present study, common carp (Cyprinus carpio) fingerlings were selected to assess the potential risk and aquatic toxicity of meloxicam as a non-steroidal anti-inflammatory and a commonly used pharmaceutical drug. In order to evaluate meloxicam toxicological effect on haematological, antioxidant status, enzymological and histological parameters, based on its LC50 24h acute toxicity (10.05mgL-1 ), fish fingerlings were exposed to four doses of meloxicam including; 0 (control), 0.1 (low), 1 (medium) and 2mgL-1 (high) under static bioassay method for 28 days. The results showed that sublethal doses of meloxicam significantly decreased alanine aminotransferase, alkaline phosphatase, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels in comparison with the control group after 28 days (p<0.05). However, red blood cell, haematocrit, haemoglobin and malondialdehyde values in fish exposed to meloxicam significantly increased alongside its concentration (p<0.05) more than the control group after 28 days. SOD, CAT and GPX mRNA expression levels in gill, liver, kidney and brain organ of fish under meloxicam treatment were significantly down-regulated compared to the control group (p<0.05). Histopathological assessment showed the increased vacuolation in hepatocytes in liver of fish exposure to medium and high doses of meloxicam. In conclusion, meloxicam induces oxidative stress in common carp which results a disruption of physiological and health status of this species based on our current findings.

Measurement of Cyclooxygenase Products in Plasma as Markers for Inhibition of Cyclooxygenase Isoforms by Oral Meloxicam in New Zealand White Rabbits (Oryctolagus cuniculus ).

Pain management in rabbits is a challenging task that is complicated by the rabbit's ability to hide signs of distress and the limited pharmacologic data available for this species. Pharmacokinetic data has shown that in rabbits, meloxicam, a nonsteroidal anti-inflammatory NSAID, reaches plasma concentrations that are known to provide analgesia in dogs and cats; these concentrations could theoretically alleviate pain in rabbits. However, the inhibitory effects of meloxicam on cyclooxygenase (COX) isoforms have not been studied in rabbits. In this study, we measured the products of COX-1 and COX-2 after the oral administration of a single 1 mg/kg dose of meloxicam to New Zealand White rabbits (n = 6). Blood samples were collected before drug administration (T0) and then at predetermined time points over 48 h. Plasma prostaglandin E₂ (PGE₂ ) and thromboxane (TxB₂) concentrations were measured as surrogate markers for COX-1 and COX-2, respectively, by using commercial ELISA kits. After meloxicam administration, both TxB₂ and PGE₂ plasma concentrations fell significantly below baseline, with maximal mean reductions to 80% and 60% of baseline at 8 h, respectively. The reduction in PGE₂ concentrations was followed by a significant increase that moved its mean plasma concentrations toward baseline between 8 and 24 h. Adverse effects such as lethargy, inappetence, or changes in fecal production were not observed in any rabbits. In conclusion, meloxicam appeared to significantly inhibit both COX-1 and COX-2 with a time course similar to previously reported meloxicam plasma concentration-time profiles in rabbits. Our data suggest that a dosage of 1 mg/kg given orally could provide analgesia to rabbits, but a more frequent dosing interval than the currently recommended daily dosing may be required to maintain clinical efficacy.

Hepatoprotective Effects of Sukari Dates Extract (Phoenix dactylifera L.) Against ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) Profile in Male Wistar Rats After Induced by Meloxicam

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) that is frequently administered to animals as an analgesic, antipyretic, and anti-inflammatory medication. Meloxicam overdose and liver damage can occur if taken for an extended period of time without first consulting a veterinarian. Sukari dates extract can neutralize the effects of free radicals and protect the liver when taken orally. After being induced by a toxic dose of meloxicam, the purpose of this study is to demonstrate that the administration of sukari dates extract may reduce the profile of ALT and AST. 24 male wistar rats were used in this laboratory experiment, which was divided into four groups (n=6). Positive control group (K2) received 30 mg/kg BW meloxicam and 1% Na CMC, while treatment group 1 (P1) received 500 mg/kg BW sukari dates extract and 30 mg/kg BW meloxicam. Treatment group 2 (P2) received 1000 mg/kg BW sukari dates extract and 30 mg/kg BW meloxicam. The negative control group (K1) received 1% Na CMC. The study lasted for 12 days, and on the 12th day, blood samples were taken for analysis. The ALT profile decreased to 67.17 U/L and 63.00 U/L in P1 and P2, respectively, and the AST profile decreased to 142.83 U/L and 125.83 U/L. As a result, it can be concluded that toxic doses of meloxicam can cause sukari dates extract to reduce ALT and AST profiles.

Pharmacokinetics, Milk Residues, and Toxicological Evaluation of a Single High Dose of Meloxicam Administered at 30 mg/kg per os to Lactating Dairy Cattle

Adverse effects associated with overdose of NSAIDs are rarely reported in cattle, and the risk level is unknown. If high doses of NSAIDs can be safely administered to cattle, this may provide a longer duration of analgesia than using current doses where repeated administration is not practical. Meloxicam was administered to 5 mid-lactation Holstein dairy cows orally at 30 mg/kg, which is 30 times higher than the recommended 1 mg/kg oral dose. Plasma and milk meloxicam concentrations were determined using high-pressure liquid chromatography with mass spectroscopy (HPLC-MS). Pharmacokinetic analysis was performed by using noncompartmental analysis. The geometric mean maximum plasma concentration (Cmax) was 91.06 µg/mL at 19.71 h (Tmax), and the terminal elimination half-life (T1/2) was 13.79 h. The geometric mean maximum milk concentration was 33.43 µg/mL at 23.74 h, with a terminal elimination half-life of 12.23 h. A thorough investigation into the potential adverse effects of a meloxicam overdose was performed, with no significant abnormalities reported. The cows were humanely euthanized at 10 d after the treatment, and no gross or histologic lesions were identified. As expected, significantly higher plasma and milk concentrations were attained after the administration of 30 mg/kg meloxicam with similar half-lives to previously published reports. However, no identifiable adverse effects were observed with a drug dose 30 times greater than the industry uses within 10 days of treatment. More research is needed to determine the tissue withdrawal period, safety, and efficacy of meloxicam after a dose of this magnitude in dairy cattle.

Assessment of Dose Dependent Toxicity of Meloxicam in Gallus Domesticus

The main objective of the study was to investigate long term use of meloxicam on avian species especially on Gallus domesticus. Animals were divided into 4 groups each having 5 animals. Group I was control and was fed normal diet (maize, grains and millet). Group II was treated with low dose of meloxicam for 15 days. Group III was treated with low dose of meloxicam for 30 days. Group IV was treated with low dose of meloxicam for 60 days. The effect was studied specially on hepatic and renal functions. Meloxicam was given at low dose (0.1 mg/kg body weight) to treatment groups for 15, 30 and 60 days. For biochemical estimation blood and serum were collected by sacrificing animals. Tissues of vital organs were fixed for histological examination. Long term administration of meloxicam cause variation in liver and kidney functioning. No significant change was observed in organ weight of treated groups as compared with control. No significant changes were observed in treated groups as compared to control in hematological parameters, biochemical parameters and lipid profile except SGOT, SGPT and alkaline phosphate in these parameters significant increase was observed. Significant changes were also observed in antioxidant analysis of treated groups as significant increase was observed in LPO and significant decrease in FRAP concentration was observed which signifies the results of histological changes especially in kidney and liver. Changes in histology of treated groups showed effect on kidney and liver as reduction (shrinkage) in glomerulus size and changes in histoarchitecture of central vein in liver of treated group was observed as compared to control group other histological examinations were normal. From results this can be concluded that long term low dose treatment of meloxicam has altered the histoarchitecture of liver and kidney of Gallus domesticus.

MELOXICAM-INDUCED GASTROPATHY IN DOGS: CLINICAL, BIOCHEMICAL, ENDOSCOPIC FEATURES AND TRIALS FOR PREVENTION

This study was conducted to evaluate and to compare the clinical, hemato-biochemical and endoscopic aspects of gastropathy in dogs treated with meloxicam alone or incombination with esomeprazole and misoprostol. Twenty baladi healthy dogs were included in the experimental study. Dogs were divided into four groups each group consisting of five animals; Group I (control group), the group that does not receive any medication. Meloxicam treated groups divided into: Group II which received meloxicam at a dose of 0.2 mg/kg BWT per OS /24 hr. Group III animals received the same previous dose of meloxicam and esomeprazole at a dose of 1mg/kg BWT per OS /24 hr. Group IV animals received the same dose of meloxicam and misoprostol 3μg /kg BWT per OS tid. Upon drug administration, dogs were kept under observation for 14 consecutive days. Clinical and hemato-biochemical analysis were evaluated across time (T0, T3, T7, T10 and T14). The image analysis of the gastroscopic examination was evaluated across time (T0, T7 and T14), endoscopic examinations were applied to all animals in four groups at three time points (T0, T7, and T14), endoscopic lesions were scored by use of a 5-point scale. Clinically, the most common clinical sings in dogs with Meloxicam induced- gastropathy were inappetence to anorexia, hematemesis, melena, abdominal pain and weakness, the specific endoscopic lesions of gastropathy were gastric erosion, hemorrhage and ulcers. Serum gastrin concentration is a biochemically sensitive indicator of gastropathy. The overall results concluded that meloxicam-induced gastropathy was more severe in group II compared to groups III and group IV. The proton pump inhibitor (esomeprazole) was more effective and better tolerated than misoprostol.

Dosage exploration of meloxicam according to CYP2C9 genetic polymorphisms based on a population pharmacokinetic-pharmacodynamic model.

Meloxicam, used for treating inflammatory diseases, shows large differences in metabolism according to CYP2C9 genetic polymorphisms; however, there are few studies on dose regimen setting based on quantitative predictions. The aim of this study was to determine the appropriate meloxicam dose regimen for each genotype through population pharmacokinetic-pharmacodynamic modeling of meloxicam by considering CYP2C9 genetic polymorphisms. For modeling, previously reported pharmacokinetic (plasma concentration)-pharmacodynamic (inhibition of thromboxane B2 generation) data of meloxicam were collected for CYP2C9 genetic polymorphisms (n=43). And these data were mainly used in the modeling process. Through simulations of the established models, steady-state pharmacokinetic-pharmacodynamic profiles were obtained according to meloxicam multiple exposures for each CYP2C9 genotype, and predictions were made based on dose regimen changes. Genetic polymorphisms of CYP2C9 were identified as key covariates that significantly affected pharmacokinetic variability of meloxicam between individuals. The developed meloxicam population pharmacokinetic-pharmacodynamic model predicted pharmacokinetic results of the 7.5mg meloxicam administration groups (n=26) for CYP2C9*1/*1 and *1/*3 as an external validation. The results of model simulation revealed that the differences were 2.39-5.42 times for steady-state mean plasma concentrations and 1.21-1.71 times for the degree of inhibition of thromboxane B2 generation following multiple exposures for CYP2C9*1/*1 versus *1/*13, *1/*3, and *3/*3. This suggested that thromboxane B2 inhibition following increased plasma exposure to meloxicam differed significantly according to CYP2C9 genetic polymorphisms. The dose of meloxicam in CYP2C9*1/*13, *1/*3, and *3/*3 was randomly adjusted to 1.6-15 mg to approximate the mean thromboxane B2 inhibition for CYP2C9*1/*1 at steady state, the dose intervals varied from 24 h to 48 h. The results suggested that clinical dose adjustment of meloxicam would be necessary to account for CYP2C9 genetic polymorphisms and reduce side effects. This study suggests a clearer direction for setting up clinical therapy based on personalized medicine and quantitative predictions for meloxicam.

Effects on hematology and blood biochemistry profile of intramuscular meloxicam injection in Brahminy kite and Barn owl.

Meloxicam is used widely for exotic animal analgesia, but its toxicity in common raptor species in Thailand is unclear. This study evaluated the single-dose effect of intramuscular meloxicam in common raptor species in Thailand for short-term and long-term periods. Twenty-two raptors were administered a single 1 mg/kg dose of meloxicam individually via intramuscular injection. The following were evaluated: clinical appearance, body weight, body condition score, body temperature, fecal appearance, complete blood cell count, and biochemistry panel before (day 0) and after the injection (1, 7, and 30 days). The collected samples were categorized into three groups: Brahminy kite (Haliastur indus) (n = 10), adult Barn owl (Tyto javanica) (n = 4), and juvenile Barn owl (n = 8). None of the raptors in the study groups showed any abnormalities. The hematological profiles were significantly different in the short-term period (day 1 and day 7). The creatinine, aspartate aminotransferase, and creatinine kinase increased in several groups. On the other hand, the packed cell volume decreased in the Brahminy kite and juvenile Barn owl groups. According to the findings, an intramuscular injection of 1 mg/kg meloxicam affected the blood biochemistry panel of the muscle, but the affected raptors recovered within one week. An intramuscular injection of meloxicam at a single 1 mg/kg dose in Brahminy kites and Barn owls was not associated with the morbidity, hepatotoxicity, gastrointestinal toxicity, and nephrotoxicity in the short- and long-term periods.

High-dose Meloxicam Provides Improved Analgesia in Female CD1 Mice: A Pharmacokinetic and Efficacy Study.

Meloxicam is a nonsteroidal anti-inflammatory analgesic drug that is often used in mice. However, doses of 1 to 5 mg/kg given twice daily were recently reported to provide inadequate analgesia. Some studies suggest that doses of up to 20 mg/kg may be necessary for adequate pain management. We investigated the analgesia provided by a high-dose of meloxicam in female CD1 mice. Pharmacokinetic analyses demonstrated that a subcutaneous injection of 10 mg/kg or 20 mg/kg of meloxicam produced therapeutic plasma concentrations for at least 12 h. Ovariectomies via ventral laparotomy were performed to assess analgesic efficacy. Mice were treated immediately before surgery with a high-dose of 10 mg/kg, a low-dose of 2.5 mg/kg, or saline, followed by every 12 h for 36 h. At 3, 6, 12, 24, and 48 h after surgery, mice were assessed for pain based on the following behaviors: distance traveled, time mobile, grooming, rearing, hunched posture, orbital tightening, and von Frey. Initially, some mice received a 20-mg/kg loading dose followed by 10 mg/kg every 12 h. This regimen caused severe morbidity and mortality in 2 mice. Subsequently, this regimen was abandoned, and mice assigned to the high-dose group received 10 mg/kg every 12 h. Mice that received the 10-mg/kg dose after surgery showed less orbital tightening between 3 to 6 h and reduced frequency of hunched posture for 48 h compared with mice that received either the low-dose or saline. However, mice were significantly less mobile for 6 to 12 h after surgery regardless of treatment. These data indicate that a meloxicam dose of 10 mg/kg every 12 h provides better analgesia than a 2.5-mg/kg dose but does not completely alleviate pain.

Effects of a Multimodal Approach Using Buprenorphine with/without Meloxicam on Food Intake, Body Weight, Nest Consolidating Behavior, Burrowing Behavior, and Gastrointestinal Tissues in Postoperative Male Mice.

Distress affects animal welfare and scientific data validity. There is a lack of reports on the effects of multimodal analgesic approaches in mice. In this study, under the hypothesis that a multimodal analgesic protocol using buprenorphine with meloxicam has analgesic effects, we evaluated the effects of a multimodal analgesic protocol using buprenorphine with meloxicam on the well-being of mice during analgesic administration by changing the dosage of meloxicam. A total of 42 Slc:ICR male mice were categorized into nonsurgical and surgical groups (7 mice per group) and treated with an anesthetic (isoflurane) and analgesics (buprenorphine ± meloxicam). Analgesics were administered for 48 h after treatment. Buprenorphine (subcutaneous; 0.1 mg/kg/8 h) and meloxicam (subcutaneous; 0, 2.5, or 5 mg/kg/24 h) were administered twice. Body weight, food intake, nest consolidation score, and latency to burrow were evaluated. A significant decrease in food intake was observed 24 h after treatment, while a significant increase was observed 48 h post-treatment in all groups. Body weight showed a decreasing trend but was not significantly reduced. Furthermore, stomach, duodenum, and jejunum tissues showed no morphological abnormalities. Significant differences in burrow diving scores and the latency to burrow were observed between some groups, but these were not regarded as a consequence of the surgery and/or the meloxicam dose. When buprenorphine and meloxicam were combined, administering up to 5 mg/kg/day of meloxicam for 48 h to male mice after abdominal surgery had no significant negative effects on any tested parameters. In conclusion, a multimodal analgesic protocol of buprenorphine with meloxicam is among the options for increasing well-being in mice following abdominal surgery.

Changes in rabbit lymphocyte subpopulations and activation following long-term administration of meloxicam

Meloxicam is a commonly used analgesic in rabbits. However, its possible impact on lymphocyte subpopulations remained unknown. The aim of the study was to investigate a possible effect of long-term administration of meloxicam on rabbit lymphocyte subpopulations. The study included 8 rabbits given meloxicam orally once daily (1 mg/kg BW) for 14 days and 8 rabbits as a control group. Peripheral blood samples were collected on day 0 (before the first dose of meloxicam), day 3, 7 and 14. Samples were evaluated with a haematology analyser and a flow cytometer. A significant decrease in T: B cell ratio was found in all samples taken during meloxicam administration compared to day 0, as well as in comparison with the control group (P < 0.01). A significant increase (P < 0.05) in proportion of CD5 +CD8 + lymphocytes occurred by day 3. Subsequently, although the values slightly decreased, they still remained elevated throughout all the experiment compared to the values from day 0 (P < 0.05). A slight decrease in T and B cell activation (CD5 +CD25 + and IgM+CD25 +) noticed by day 3, declined during the next days of administration and became more and more significant (finally, P = 0.0078). Since a high significant decrease (P < 0.01) in both T and B cell activation as well as a significant increase (P < 0.05) in CD5 +CD8 + T cells proportion were observed after meloxicam administration, a predicted effect of long-term administration of meloxicam on rabbit lymphocytes was confirmed.

Pharmacokinetics and Egg Residues of Oral Meloxicam in Bantam Cochin Chickens.

Backyard poultry are commonly treated in veterinary hospitals; however, there is limited information regarding appropriate dosing of medications and withdrawal times for eggs. Six healthy adult bantam Cochin hens were given a single oral dose of meloxicam (1 mg/kg). Meloxicam plasma concentrations and egg residues were analyzed by high-performance liquid chromatography. Noncompartmental analysis was used to calculate pharmacokinetic parameters. The apparent terminal half-life, maximum concentration, and time to maximum concentration were 5.94 ± 0.92 hours, 7.03 ± 2.68 µg/mL, and 2.83 ± 1.33 hours, respectively. Meloxicam was detected in egg whites for 4.8 ± 1.5 days and egg yolks for 9.8 ± 2.4 days. Results were compared with previous studies in white leghorn and Columbian Wyandotte hens. Bantam Cochin hens demonstrated a significantly longer mean apparent terminal half-life, greater area under the curve, smaller elimination rate constant, and longer egg residue times compared with white leghorn hens. However, the pharmacokinetic results from the bantam Cochin hens did not significantly differ from those reported for the Columbian Wyandotte hens. Until pharmacodynamic studies can be performed, dosing of oral meloxicam in bantam Cochins should follow recommendations for Columbian Wyandotte hens to reduce the likelihood of adverse effects. These results better inform appropriate dosing of meloxicam in domestic hens, as well as recommended withdrawal times for egg consumption.

The histological effect of the injection of nonsteroidal anti-inflammatory drugs on sciatic nerve of rats

The ongoing work aims to compare the effect of extraneural and intraneural injection of therapeutic doses of meloxicam and diclofenac sodium on the sciatic nerve of rats. Six groups of adult albino rats were used with five animals per group. Control group (A), group (B), and group (C) received a single extraneural injection of normal saline (NS) 0.25 ml/kg/rat, meloxicam (M) 0.11 mg/kg/0.25ml/rat and diclofenac sodium (V) 1.1 mg/kg/0.25ml/rat respectively. In contrast, control group (D), group (E), and group (F) received a single intraneural injection of the same doses of normal saline, meloxicam, and diclofenac sodium, respectively. Histological evaluation reveals an increased thickening of epineurium, dilatation, congestion of epineurial blood vessels, intrafascicular edema, axonal degeneration, myelin degeneration, and vacuolization in group (C) which was higher than those in the group (B). These changes were also greater in group (F) compared to groups (D) and (E). The histopathological changes of the sciatic nerve were greatest in the case of intraneural injection of saline, meloxicam, and diclofenac sodium, which means that the damaging effect of intraneural injection of the drug was greater than the extraneural injection of the same drug. It is concluded that extraneural and intraneural injections of therapeutic doses of meloxicam cause less damage to the sciatic nerve compared to diclofenac sodium. Thus it is considered to be more secure than diclofenac sodium after intramuscular injection. Sciatic nerve injury can occur following intramuscular injection into the gluteal region, particularly if the needle hits the nerve.

Effect of plane of nutrition and analgesic drug treatment on wound healing and pain following cautery disbudding in preweaning dairy calves

The objective of this study was to determine the effect of a biologically normal plane of nutrition compared with a limited plane on the primary outcome wound healing, and one dose of nonsteroidal anti-inflammatory drug (NSAID) compared with 2 on the secondary outcomes: lying behavior, haptoglobin concentrations, and mechanical nociceptive threshold (MNT) in calves disbudded via cautery iron. Eighty female Holstein calves were enrolled at birth, individually housed, and fed via a Calf Rail system (Förster Technik). A 2 × 2 factorial design was used to assess the effect of plane of nutrition and an additional NSAID. Calves were randomly assigned to a biologically normal plane of nutrition (BN; offered up to 15 L/d) or a limited plane (LP; offered up to 6 L/d) and to receive one or 2 doses of meloxicam. All calves received a lidocaine cornual nerve block and a subcutaneous injection of meloxicam 15 min before cautery disbudding at 18 to 25 d of age, and half the calves received an additional injection of meloxicam (0.5 mg/kg) 3 d after disbudding. Tissue type present, wound diameter, and wound depth were evaluated 2 times per week for 7 to 8 wk as measures of wound healing, lying behavior was recorded beginning 1 to 2 wk before disbudding until 7 to 8 wk after as a behavioral indicator of pain, haptoglobin concentrations were measured once per day for 7 d after disbudding, and MNT was evaluated 2 times/wk for 3 wk. Survival analyses were analyzed using Cox regression models (wound healing) and continuous data were analyzed using mixed-effect linear regression models. Only 12% of horn buds were completely healed by 7 to 8 wk after disbudding and 54% had re-epithelized at this time. At any time, wounds from BN calves were more likely to have had re-epithelization occur compared with wounds from LP calves (hazard ratio: 1.93, 95% CI: 1.18-3.14). Wounds from calves that received only one dose of NSAID were more likely to have re-epithelization occur, compared with wounds from calves given 2 doses (hazard ratio: 1.87, 95% CI: 1.15-3.05). Wounds from BN calves had smaller diameters and depths over time beginning on wk 3 compared with LP calves. Wounds from calves that received an additional NSAID had larger diameters and depths over time beginning on wk 4 and 3 respectively, compared with calves that only received one dose of NSAID. Calves that received an extra NSAID tended to be less sensitive 7, 10, and 17 d after disbudding compared with calves that only received one dose and spent less time lying in the week after disbudding. Calves on the BN milk program were more active compared with LP calves with lower lying times, fewer lying bouts per day, and longer average lying bouts. Our results indicate that a BN milk feeding program for calves can result in faster healing times and more activity, and that providing an extra NSAID 3 d after disbudding appears to slow the healing process but may result in less pain experienced by the calf 1 to 2 wk after the procedure. This study is also among the first to demonstrate that after the complete removal of the horn bud, wounds can take more than 8 weeks to re-epithelize and fully heal.

Wintertime pharmacokinetics of intravenously and orally administered meloxicam in semi-domesticated reindeer (Rangifer tarandus tarandus)

ObjectiveTo investigate the pharmacokinetics of orally and intravenously (IV) administered meloxicam in semi-domesticated reindeer (Rangifer tarandus tarandus). Study designA crossover design with an 11 day washout period. AnimalsA total of eight young male reindeer, aged 1.5–2.5 years and weighing 74.3 ± 6.3 kg, mean ± standard deviation. MethodsThe reindeer were administered meloxicam (0.5 mg kg–1 IV or orally). Blood samples were repeatedly collected from the jugular vein for up to 72 hours post administration. Plasma samples were analysed for meloxicam concentrations with ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry. Noncompartmental analysis for determination of pharmacokinetic variables was performed. ResultsThe pharmacokinetic values, median (range), were determined. Elimination half-life (t½) with the IV route (n = 4) was 15.2 (13.2–16.8) hours, the volume of distribution at steady state was 133 (113–151) mL kg−1 and clearance was 3.98 (2.63–5.29) mL hour–1 kg–1. After oral administration (n = 7), the peak plasma concentration (Cmax) was detected at 6 hours, t½ was 19.3 (16.7–20.5) hours, Cmax 1.82 (1.17–2.78) μg mL–1 and bioavailability (n = 3) 49 (46–73)%. No evident adverse effects were detected after either administration route. Conclusions and clinical relevanceA single dose of meloxicam (0.5 mg kg–1 IV or orally) has the potential to maintain the therapeutic concentration determined in other species for up to 3 days in reindeer plasma.