Given that oxidative stress (OS) occurs as one of the complications of general anesthesia and surgical procedures, practicing the best and safest anesthesia regimen can have a significant share in various surgeries. So, this study compared the effects of non-steroidal anti-inflammatory drugs (NSAIDs) such as ketoprofen (KTP) and meloxicam (MLX) on OS through the glutathione pathway after the ketamine-xylazine (K-X) anesthesia and ulcer induction in rats to suggest post-operative regimens with promising analgesic and anti-inflammatory effects. 80 healthy adult male Wistar rats, were examined in this study. To obtain the baseline value cardiac blood collected of five rats, and the remaining 75 animals were randomized into three groups of 25, including (i) the control group receiving physiological serum, (ii) the experimental group 1 taking KTP, (iii) the experimental group 2, administered by MLX and all three groups received K-X combination IP after 30 min. Then, a full-thickness ulcer was induced under standard conditions, and the blood samples were collected from groups at T0, T30m, T60m, T24h, and T48h. The serum levels of the desired markers were measured. The study results revealed that the administration of K-X as an anesthetic agent made some changes in the markers of the OS-related glutathione (GSH) pathway. Moreover, KTP and MLX, significantly (p < 0.05) augmented the reduced GSH (rGSH), lowered the GSSG, increased the total values of the glutathione disulfide (GSSG) and the rGSH, reduced the rGSH/GSSG ratio, and accelerated the glutathione peroxidase (GPx) activity, but they had high inhibitory effects on the glutathione reductase (GR). Accordingly, both drugs could maintain the balance between the OS markers, caused by general anesthesia. In general, KTP can be a suitable regimen in surgeries wherein analgesia is of importance for less than 24 h, but MLX can be a preferable option if longer analgesia is needed for more than 24 h.

BACKGROUND: Grapiprant is a novel anti-inflammatory drug approved for the treatment of pain associated with osteoarthritis in dogs.
OBJECTIVE: Compare the efficacy of grapiprant vs meloxicam for the management of postoperative joint pain in dogs.
METHODS: Forty-eight dogs presented with cranial cruciate ligament disease and treated by tibial plateau leveling osteotomy (TPLO) between May 2020 and May 2022.
METHODS: In this randomized, double blinded, prospective clinical trial, client-owned dogs with naturally occurring unilateral cruciate ligament rupture were enrolled on the day of surgery. The day after surgery, all animals received a subcutaneous injection of 0.2 mg/kg of meloxicam and were randomly assigned to receive either oral grapiprant (2 mg/kg) or meloxicam (0.1 mg/kg), once a day for 14 days, in a blinded manner. The primary endpoint of the study was the pain severity (PSS) and interference (PIS) scores, assessed by the Canine Brief Pain Inventory (CBPI) at day 3, 7, 10 and 15 after the surgery.
RESULTS: Three days after surgery, grapiprant treated dogs had lower PSS compared to meloxicam treated dogs with a mean ± SD of 2.76 ± 0.18 vs 3.25 ± 0.23, respectively (difference of -0.49 [95% CI -0.94 to -0.04], P = .032). Pain Interference Score was also lower in grapiprant group at day 3 (4.11 ± 0.18 vs 4.69 ± 0.16 in meloxicam group [difference of -0.58 {95% CI -1.03 to -0.13}, P = .013]) and at day 10 (2.23 ± 0.13 vs 2.72 ± 0.28 [difference of -0.49 {95% CI -0.92 to -0.01}, P = .049]).
CONCLUSIONS: Our study supports the use of grapiprant as an alternative analgesic to meloxicam for management of postoperative joint pain in dogs.

BACKGROUND: Umbilical outpouchings (UOs) are common in Danish pigs. Neonatal antibiotics are therefore used with the hope of reducing umbilical infections and subsequently UOs. However, the effect of neonatal antibiotics on preventing UO has been the subject of mixed conclusions, and secondly, treating all animals with antibiotics might exacerbate the development of antimicrobial resistance. This study analysed the effects of different treatments on the prevalence of umbilical outpouchings and mortality from birth to nursery unit. All treatment was on the day of birth. The groups were: a negative control group, an antibiotic group receiving amoxicillin, and an experimental group where the piglets had their umbilical cord disinfected with chlorhexidine, followed by tying and clipping, and lastly, injection with meloxicam. The pigs were examined six weeks after weaning, and all pigs that died during the study were autopsied.
RESULTS: There were 5494 pigs divided across the three groups. There were no statistically significant differences in UO prevalence between the groups: control 3.9%, antibiotic 4.2%, and experimental 4.0% (p = 0.87). The only variable affecting the prevalence of UOs in this study was sex with females being at higher risk. There were no statistically significant differences in mortality between the groups from birth until departure from the nursery unit: control 22.9%, antibiotic 21%, and experimental 21.4% (p = 0.33). The variables affecting mortality were sex, intrauterine growth restriction (IUGR), birth weight, and cross fostering. Males had higher odds of dying, as had piglets recorded with some degree of IUGR. Also, low birth weight increased the odds of dying for all weight quartiles compared to the fourth (the heaviest piglets > 1.6 kg), as well as cross fostering increased the odds ratio of dying.
CONCLUSIONS: This study found no significant differences in the prevalence of UOs and mortality following different treatments at birth. The study showed that the prevalence of UO and mortality was not reduced following the administration of amoxicillin or meloxicam in combination with disinfection and tying of the umbilical cord.

UNASSIGNED: This study aimed to assess how effective an oral form of Cetylated fatty acids compounds (CFA) is in improving the physical function, pain, and stiffness of individuals suffering from knee osteoarthritis (OA) and how its effectiveness compares to that of Meloxicam, a non-steroidal anti-inflammatory drug (NSAID).
UNASSIGNED: For this parallel-arm randomised clinical trial, 48 adult patients with knee OA were divided into two groups. The intervention group was prescribed 350mg CFA capsule three times per day for 30 days. The control group was given 15mg of Meloxicam, one tablet daily for ten days. Patients were instructed to fill out the Oxford Knee Score (OKS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Visual Analog Scale (VAS). Data were obtained before the administration of the first dose (considered baseline or t0), and two (t1), four (t2), and eight (t3) weeks after the final dose of each intervention.
UNASSIGNED: No significant differences were observed in total WOMAC and OKS scores between the two groups at t1, t2, or t3. However, both groups had significant improvements in their OKS, VAS, and total WOMAC scores compared to their baselines (t0). No adverse events were noted in the CFA group.
UNASSIGNED: Improvements in pain intensity and overall physical function were reported in the CFA group. Oral CFAs could safely benefit patients with knee OA.

We evaluated the effect of administration timing of meloxicam and robenacoxib on renal function, platelet cyclo-oxygenase and perioperative analgesia in 60 cats undergoing ovariohysterectomy, in a prospective randomized blinded controlled study. Twelve cats were randomly allocated to one subcutaneous treatment group: meloxicam (0.2 mg/kg) or robenacoxib (2 mg/kg) at admission (MA, RA), at induction (MI, RI) and robenacoxib at the end of surgery (RE). All cats received the same anaesthesia protocol. Plasma renin activity (PRA), plasma creatinine, drug concentrations and serum thromboxane (TxB2) were measured sequentially. Anaesthesia significantly increased PRA, as activity at end of the surgery was higher than 2 h later (mean ± SD: 26.6 ± 2.8 versus 10.0 ± 3.9 ng/mL/h). PRA remained higher at 2 h post-surgery in admission groups compared to induction groups (p = .01). Serum TxB2 was lower with meloxicam than robenacoxib (p = .001), and was lower in the MA than each robenacoxib group at catheter placement. Admission groups (16/24 from RA and MA groups) received earlier rescue analgesia than other groups (p = .033). In conclusion, the renin-angiotensin system was activated during anaesthesia despite cyclo-oxygenase inhibition, possibly due to hypotension or surgical stimulation. There was no effect of drug or timing on the markers of renal function but one cat receiving meloxicam at induction had suspected IRIS grade II acute kidney injury.

BACKGROUND: QP001, a novel meloxicam formulation, has been developed to manage moderate to severe postoperative pain. This study aimed to evaluate the efficacy and safety of QP001 injections for moderate to severe pain following abdominal surgery.
METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial enlisted patients experiencing moderate to severe pain following abdominal surgery. These patients were randomized to receive either QP001 injections (30 mg or 60 mg) or a placebo pre-surgery. The primary efficacy endpoint was the total morphine consumption within 24 h after the first administration.
RESULTS: A total of 108 patients were enrolled, and 106 patients completed the study. The total morphine consumption in the QP001 30 mg group and 60 mg group, versus placebo group, were significantly lower over the following 24 h (5.11[5.46] vs 8.86[7.67], P = 0.011; 3.11[3.08] vs 8.86[7.67], P < 0.001), respectively. The total morphine consumption in the QP001 30 mg and 60 mg groups, versus placebo group, was also significantly decreased over the following 48 h, including the 24-48 h period (P ≤ 0.001). The QP001 30 mg and 60 mg groups, versus placebo, showed a significant decrease in the area under the curve for pain intensity-time as well as a significant decrease in the effective pressing times of the analgesic pump over the 24 h and 48 h periods (P < 0.05). The QP001 groups, versus placebo, show no significant different in Adverse Events or Adverse Drug Reactions (P > 0.05).
CONCLUSIONS: Preoperative/preemptive QP001 provides analgesia and reduces opioid consumption in patients with moderate to severe pain following abdominal surgery, while maintaining a favorable safety profile.

UNASSIGNED: Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of QP001 in Chinese healthy subjects.
UNASSIGNED: The trial consisted of three parts. Part I was a two-period crossover study to evaluate bioavailability, in which 10 healthy were either intravenously infused with 15mg QP001 (test) or orally given 15mg MobicⓇ (reference). Part II was a single-arm design to assess the pharmacokinetic (PK) characteristics after 30 mg single- and multiple-dose QP001 in 10 subjects. In part III, we investigated the PKs and tolerability of QP001 at a high dose (60 mg) in another 10 subjects. The PK parameters and treatment-emergent adverse events (TEAEs) were evaluated.
UNASSIGNED: A total of 30 subjects were enrolled in the study. QP001 was well tolerated and safe without significant TEAEs in all three study parts. The PK characteristics of QP001 were linear following a single-dose range of 15-60 mg (Cmax and AUC0-t were 5.82-17.66 μg/mL and 58.08-251.17 μg∙h/mL, respectively). After five consecutive daily 30 mg doses, the accumulation index was around 1.98, which indicated a minimal accumulation of QP001. Compared to the tablet dosage form, the relative bioavailability of QP001 reached 116.85%. Additionally, the PK profile of QP001 showed no gender difference.
UNASSIGNED: QP001 was well tolerated in healthy Chinese subjects after single ascending doses up to 60 mg and multiple-dose of 30 mg. Based on the PK and safety results, QP001 is a promising once-daily intravenous COX-2 inhibitor candidate for managing pain.
UNASSIGNED: The trial is registered at chinadrugtrials.org.cn (ChiCTR2100047884).

Caustic paste disbudding (CPD) is widely utilized for calves, which has been known to result in adverse effects on the calves and ethical concerns related to animal welfare, despite the use of local anesthetics. The administration of meloxicam has been demonstrated to provide benefits in alleviating pain and inflammation in juvenile calves under 9 d old and subjected to CPD. Nonetheless, there is a scarcity of literature documenting the beneficial impact of meloxicam in alleviating pain in calves aged over 9 d that have undergone CPD. Therefore, the objective of this clinical trial was to evaluate the efficacy of administering meloxicam and lidocaine for cornual nerve block together in mitigating the deleterious effects of CPD, as opposed to using lidocaine alone in calves older than 9 d. Thirty Holstein calves, aged between 10 and 21 d, were enrolled and randomly assigned to 1 of 2 treatments: lidocaine alone (Placebo), lidocaine and normal saline treatment before CPD, and lidocaine plus meloxicam, lidocaine and 0.5 mg/kg of meloxicam treatment prior to CPD. The researchers were blind to the treatment of calves to control the subjective error. The occurrences of actions associated with pain, which included head shaking, head rubbing, ear flicking, tail flicking, kicking, and head passing through the fence, were recorded. Physiological performance, including the respiration rate, heart rate, rectal temperature, mechanical nociceptive threshold (MNT), food intake, and daily activity level, was monitored. Hematological conditions were ascertained through the use of routine blood tests and enzyme-linked immunosorbent assay. The generalized linear mixed model was employed to analyze the data. The research findings revealed that applying the CPD procedure significantly elevated the frequencies of tail flicking, head shaking, and kicking, resulted in increases in respiratory rate, heart rate, daily active steps, and food intake and a decrease in MNT, and led to alterations in hematological markers, including platelet counts, mean platelet volume, prostaglandin E2, constitutive nitric oxide synthase, and hydroxyl radical. Considerable benefits, such as lower heart rates, higher food intake, and MNTs, as well as lower levels of white blood cell counts, lymphocyte counts, hemoglobin, mean platelet volume, prostaglandin E2, tumor necrosis factor-α, constitutive nitric oxide synthase, malondialdehyde, and hydroxyl radical, were observed in the calves that received meloxicam treatment in response to CPD. The findings of the study indicate that the co-administration of lidocaine and meloxicam provides obvious benefits in mitigating pain, inflammation, and oxidative stress in calves aged over 9 d and undergoing CPD. This endorses the use of meloxicam during the disbudding and dehorning procedures of calves.
Caustic paste disbudding (CPD) is a widely used practice in the cattle industry, yet there is a shortage of literature on the effects of meloxicam on calves aged 10 to 21 d who have undergone this procedure. In this clinical trial, we conducted a comparative analysis of the pain-related behavioral, physiological, and hematological performance of calves that were administered with either lidocaine plus normal saline (n = 15) or lidocaine plus meloxicam (n = 15) before undergoing disbudding operations. The findings demonstrated that the CPD operation had a significant impact on the pain-related behavior, physiological functions, and serum anti-inflammatory and antioxidative markers of the calves. On the other hand, the administration of meloxicam had notable advantages for the calves by enhancing the physiological and hematological parameters.

Injectable non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to queens undergoing ovariohysterectomy (OVH), but the requirement for postoperative administration is unclear and practices vary. Existing studies assessing efficacy rely on pain scoring by experienced clinicians. However, following OVH, most cats are discharged within hours of recovery.
Cats undergoing OVH were randomly assigned to two treatment groups: MEL and ROB. Cats in the MEL group (n = 76) received meloxicam (0.2 mg/kg) and those in the ROB group (n = 65) received robenacoxib (2 mg/kg). Owners were contacted by a blinded assessor 3 days postoperatively and asked to identify physical or behavioural changes and to assign pain scores using a numerical rating scale.
More cats in the ROB group displayed abnormal behaviours than cats in the MEL group (p = 0.03). Most owners assigned a pain score of 0 (72%) (n = 101), but pain scores were significantly higher in the ROB group than in the MEL group (p = 0.005).
Methods of owner assessment of pain in cats have not been validated.
Both meloxicam and robenacoxib are effective in controlling postoperative pain. Meloxicam may have improved efficacy in certain patient populations. Applying a blanket approach to prescribing NSAIDs to cats undergoing OVH postoperatively may not be necessary. This has safety, environmental and cost implications.

The increasing prevalence of water insoluble or poorly soluble drugs calls for the development of new formulation methods. Common approaches include the reduction of particle size and degree of crystallinity. Pulsed laser ablation is a clean technique for producing sub-micrometre sized drug particles and has the potential to induce amorphization. We studied the effect of femtosecond pulsed laser ablation (ELI ALPS THz pump laser system: λc = 781 nm, τ = 135 fs) on meloxicam in distilled water and in air. The ablated particles were characterized chemically, morphologically and in terms of crystallinity. We demonstrated that femtosecond laser ablation can induce partial amorphization of the particles in addition to a reduction in particle size. In the case of femtosecond pulsed laser ablation in air, the formation of pure meloxicam spheres showed that this technique can produce amorphous meloxicam without the use of excipients, which is a unique result. We also aimed to describe the ablation processes in both investigated media.