Meloxicam Concentrations Research Articles

PSIII-28 Evaluation of tissue and plasma meloxicam concentrations using a microneedle patch for drug delivery

Abstract The objective of this study was to evaluate plasma and ear tissue meloxicam concentrations when the drug was delivered using two different formulations of a microneedle patch placed on the back of the ear. Nursing pigs [n = 10; body weight (BW) = 3.64 ± 0.32 kg) from 1 litter were assigned randomly to 1 of 2 treatment groups. Patches delivered 2.5 mg of meloxicam/kg BW to pigs regardless of formulation, with the differences in patches being based on type of polymer located on the microneedles and base of the patch. Treatment groups were: 1) pigs receiving a microneedle patch with collagen, polyvinyl alcohol (PVA), and meloxicam on the microneedles, with PVA and chitosan on the base (n = 6 pigs; Patch A); and 2) pigs receiving a microneedle patch with chitosan, PVA, and meloxicam on the microneedles, with collagen and PVA on the base (n = 4 pigs; Patch B). During the study, pigs remained in the crate with the sow and littermates. An Estrotect Breeding Indicator strip was used to adhere the microneedle patch on the ear of the pigs. Blood was collected at study initiation prior to patch administration (0 h) and 24 and 48 h for plasma meloxicam analysis. To evaluate tissue meloxicam concentrations, 3 pigs that received Patch A and 2 pigs that received Patch B were humanely euthanized after blood collection and patch removal at 24 and 48 h, with the entirety of the ear removed for analysis. Statistical analyses were performed using the MIXED procedure of SAS 9.4 (Cary, NC) to assess the effects of treatment, hour, and treatment × hour interaction. Statistical significance was determined at P ≤ 0.05, with tendencies at 0.05 < P ≤ 0.1. There were no differences (P = 0.83) between patch formulations for tissue meloxicam concentrations (Patch A = 6.55 ± 2.12 ng/mg; Patch B = 7.32 ± 2.60 ng/mg). Plasma concentrations were not detectable at any time point, but tissue concentrations of meloxicam were detectable for pigs that received either patch formulation at 24 (5.44 ± 2.37 ng/mg) and 48 h (8.42 ± 2.37 ng/mg). There were no differences (P = 0.41) between patch formulations for tissue meloxicam concentrations at either timepoint, nor was there an interaction of patch formulation and hour (P = 0.73). It is unknown why the meloxicam did not diffuse from the ear tissue into the plasma; however, further studies will focus on applying the microneedle patch at different areas on the animal to allow for optimal diffusion through the skin and into blood circulation for pain mitigation in livestock animals.

A Multicomponent Microneedle Patch for the Delivery of Meloxicam for Veterinary Applications.

This study evaluates the use of poly(vinyl alcohol), collagen, and chitosan blends for developing a microneedle patch for the delivery of meloxicam (MEL). Results confirm successful MEL encapsulation, structural integrity, and chemical stability even after ethylene oxide sterilization. Mechanical testing indicates the patch has the required properties for effective skin penetration and drug delivery, as demonstrated by load-displacement curves showing successful penetration of pig ear surfaces at 3N of normal load. In vitro imaging confirms the microneedle patch penetrates the pig's ear cadaver skin effectively and uniformly, with histological evaluation revealing the sustained presence and gradual degradation of microneedles within the skin. Additionally, in vitro drug diffusion experiments utilizing ballistic gel suggest that microneedles commence dissolution almost immediately upon insertion into the gel, steadily releasing the drug over 24 h. Furthermore, the microneedle patch demonstrates ideal drug release capabilities, achieving nearly 100% release of meloxicam content from a single patch within 18 h. Finally, in vivo studies using pigs demonstrate the successful dissolution and transdermal drug delivery efficacy of biodegradable microneedle patches delivering meloxicam in a porcine model, with over 70% of microneedles undergoing dissolution after 3 days. While low detectable meloxicam concentrations were observed in the bloodstream, high levels were detected in the ear tissue, confirming the release and diffusion of the drug from microneedles. This work highlights the potential of microneedle patches for controlled drug release in veterinary applications.

Pharmacokinetics of Injectable Meloxicam and Buprenorphine in the Naked Mole-Rat (Heterocephalus glaber).

Unique characteristics of the naked mole-rat (NMR) have made it increasingly popular as a laboratory animal model. These rodents are used to study many fields of research including longevity and aging, cancer, circadian rhythm, pain, and metabolism. Currently, the analgesic dosing regimens used in the NMR mirror those used in other rodent species. However, there is no pharmacokinetic (PK) data supporting the use of injectable analgesics in the NMR. Therefore, we conducted 2 independent PK studies to evaluate 2 commonly used analgesics in the NMR: meloxicam (2 mg/kg SC) and buprenorphine (0.1 mg/kg SC). In each study, blood was collected at 8 time points after subcutaneous injection of meloxicam or buprenorphine (0 [predose], 0.25, 0.5, 1, 2, 4, 8, and 24 h). Three NMRs were used per time point for a total of 24 animals per PK study. Plasma concentrations of meloxicam were highest between 0.5 and 1 h postinjection. Levels remained above the extrapolated dog and cat therapeutic threshold levels (390 to 911 ng/mL) for at least 24 h. Plasma concentrations of buprenorphine were highest between 0.25 and 0.5 h postinjection. Levels remained above the human therapeutic threshold (1 ng/mL) for up to 21 h. No skin reactions were seen in association with injection of either drug. In summary, these data support dosing meloxicam (2 mg/kg SC) once every 24 h and buprenorphine (0.1 mg/kg SC) once every 8 to 12 h in the NMR. Further studies should be performed to evaluate the clinical efficacy of these drugs by correlating plasma concentrations with postoperative pain assessments.

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-3 Evaluation of a microneedle patch for the delivery of meloxicam in a veterinary application

Abstract In the livestock industry, animals undergo painful procedures such as castration and these practices have received increased scrutiny and concern regarding animal welfare. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used to treat pain and inflammation in livestock. Novel administration routes such as transdermal drug delivery using polymeric biodegradable microneedle patches that are being developed to deliver drugs in a less stressful method. Therefore, the objective of this study was to evaluate meloxicam plasma concentrations when drug was delivered using a microneedle patch. Nursing pigs (n = 7; body weight = 3.69 ± 1.12 kg) from 1 litter were stratified into 1 of 3 treatment groups. Treatments were: 1) 0.5 mg of meloxicam/kg of body weight via oral drench (n = 2; oral); 2) a patch devoid of meloxicam (n = 1; placebo); or 3) 2.5 mg of meloxicam/kg of body weight delivered via microneedle patch (n = 4; patch). During the study, pigs remained in the crate with the sow and littermates. Blood was collected via jugular venipuncture for plasma analysis at 0, 8, 24, 48, and 72 h. An Estrotect Breeding Indicator strip was used to adhere the microneedle patch on the ear of the pigs. Briefly, the strip was cut to the size of the ear, a microneedle patch was placed at the center, and these were applied on the pinna of the ear after blood collection at 0 h. Statistical analyses were performed using the MIXED procedure of SAS 9.4 (Cary, NC) to assess the effects of treatment, time, and treatment × time interaction. Statistical significance was determined at P ≤ 0.05, with tendencies at 0.05 < P ≤ 0.1. There was a treatment × time interaction (P = 0.0074), with the pigs that received oral meloxicam having greater meloxicam plasma concentrations at 8 h compared with pigs that received a placebo patch or a patch containing meloxicam (P < 0.0001). There were no differences in plasma meloxicam concentrations between pigs receiving a placebo patch or a patch containing meloxicam (P = 0.9). Plasma levels of meloxicam were detectable but low in pigs that received a microneedle patch (0.91 ng/mL). Research is continuing to determine the ideal microneedle patch polymer and structure that would deliver meloxicam to achieve desired plasma concentrations.

Efficacy Evaluation of Meloxicam 15mg Tablet through Bioequivalence Study in Indonesian Healthy Volunteers

Objective: The objective of this study is to compare the efficacy between the generic drug of Meloxicam 15mg Tablets produced by PT. Kimia Farma Tbk and its comparator (Movi-Cox® 15mg Tablet by PT. Boehringer Ingelheim Indonesia) by a study of bioequivalence in Indonesian healthy volunteers Methods: A randomized, single-dose, open-label, crossover two-way (2 treatments, 2 periods, and 2 sequences) under fasting condition were conducted in healthy Indonesian volunteers to evaluate bioequivalence between 2 formulations of Meloxicam 15mg tablet. This study required washout period of at least 7-days. The test and comparator drug were administered to subjects as a single oral dose. Blood samples were collected adequately (0–72 h) with 18 points to determine meloxicam concentrations in plasma using a validated LC-MS/MS analytical method. The number of subjects who participated and completed the study were 18 volunteer (9 male and 9 female). The pharmacokinetic parameters calculated in this study are AUC0-72, AUC0-inf, Cmax, tmax, and t½. The bioequivalence acceptance limit of 90% confidence interval (CI) with α = 5.00% is 80.00–125.00% for AUC and Cmax parameters. The estimation of Tmax and T½ in the bioequivalence study was based on a nonparametric statistical procedure on the original data using Wilcoxon Sign Test. Result: The results for AUC0-72 and Cmax were 108.07% (104.88-111.35) % and 105.24% (97.72-113.34) % respectively with intra-subject variability (%CV) was 5.15% for AUC0-t and 12.80% for Cmax. These results were within the regulatory acceptance limit 80.00-125.00%. Conclusion: Based on this result, it was concluded that the test formulation is bioequivalent to comparator formulation

Pharmacokinetics of meloxicam following intravenous administration at different doses in sheep.

The aim of this study is to determine the pharmacokinetic change after intravenous administration of meloxicam at doses of 0.5, 1 and 2 mg/kg to sheep. The study was carried out on six Akkaraman sheep. Meloxicam was administered intravenously to each sheep at 0.5, 1, and 2 mg/kg doses in a longitudinal pharmacokinetic design with a 15-day washout period. Plasma concentrations of meloxicam were determined using the high performance liquid chromatography-ultraviolet, and pharmacokinetic parameters were evaluated by non-compartmental analysis. Meloxicam was detected up to 48 h in the 0.5 mg/kg dose and up to 96 h in the 1 and 2 mg/kg doses. As the dose increased from 0.5 to 2 mg/kg, terminal elimination half-life, and dose normalized area under the concentration versus time curve increased and total clearance decreased. Compared to the 1 mg/kg dose, it was determined that Vdss decreased and C0.083h increased in the 2 mg/kg dose. Meloxicam provided the therapeutic concentration of >0.39 μg/mL reported in other species for 12, 48 and 96 h at 0.5, 1 and 2 mg/kg doses, respectively. These results show that meloxicam exhibits non-linear pharmacokinetics and will achieve unpredictable plasma concentrations when administered IV for a rapid effect at dose of ≥1 mg/kg in sheep.

Pharmacokinetics of meloxicam in pre-ruminant calves after intravenous, oral, and subcutaneous administration.

Meloxicam is routinely used for pain alleviation in pre-ruminant calves during husbandry procedures. The pharmacokinetics of a single dose (0.5 mg/kg) of meloxicam was investigated after intravenous (IV), subcutaneous (SC), and oral (PO) administration in 30 pre-ruminant calves. Each group included 10 calves. Oral meloxicam was administered at least 1 h after feeding. Plasma samples were collected for up to 168 h, and the meloxicam concentration was analysed with liquid chromatography and mass spectrometry, followed by a noncompartmental pharmacokinetic analysis. The maximum meloxicam concentrations in plasma were 1.91 ± 0.27 μg/mL and 1.77 ± 0.16 μg/mL after SC and PO routes, respectively. The time of maximum concentration was 7.6 ± 2.8 h after SC and 10.0 ± 5.7 h after PO administration. The approximate bioavailability of meloxicam was 97% for SC and PO routes. The elimination half-lives were 79.2 ± 12.4, 84.6 ± 24.8, and 84.8 ± 22.3 h after IV, SC, and PO routes, respectively. The results suggest that the therapeutic meloxicam concentrations in plasma that are required for pain relief in other species, such as horses, may be maintained for several days following a single dose (0.5 mg/kg) administered IV, SC, or PO in calves.

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.

Disposition kinetics of meloxicam in green sea turtles (Chelonia mydas) after intravenous and intramuscular administrations.

The pharmacokinetics were described of meloxicam (MLX) in green sea turtles (Chelonia mydas), following a single intravenous (i.v.) and intramuscular (i.m.) administrations at one of two dosages of 0.1 or 0.2 mg/kg body weight (b.w.). The sample of 20 green sea turtles was divided into four groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at pre-assigned times up to 168 h. MLX in the plasma was cleaned-up and quantified using a validated high-performance liquid chromatography method with UV detection. The concentration of MLX in the experimental green sea turtles with respect to time was pharmacokinetically analyzed using a non-compartment model. MLX plasma concentrations were quantifiable for up to 72 and 120 h after i.v. at dosages of 0.1 and 0.2 mg/kg b.w., respectively, whereas it was measurable for up to 168 h after i.m. administration at both dosages. The long elimination half-life value of MLX (28 h) obtained in green sea turtles after i.v. administration was consistent with the quite slow clearance rate for both dosages. The average maximum concentration (Cmax ) values of MLX were 1.05 μg/mL and 4.26 μg/mL at dosages of 0.1 and 0.2 mg/kg b.w., respectively, with their elimination half-life values being 37.26 h and 30.64 h, respectively, after i.m. administrations. The absolute i.m. bioavailability was approximately 110%. These results suggested that i.m. administration of MLX at a dosage of 0.2 mg/kg b.w. was likely to be effective for clinical use in green sea turtles (Chelonia mydas). However, further studies are needed to determine the pharmacodynamic properties and clinical efficacy of MLX for the treatment of inflammatory disease after single and multiple dosages.

Age-related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep.

The pharmacokinetics of meloxicam was studied in 1-, 6-, and 12-month-old sheep following a single intravenous (i.v.) dose of 1 mg/kg. The experiments were carried out when the Romanov sheep were 1 month old (7.93 ± 0.91 kg), 6 months old (27.47 ± 4.91 kg), and 12 months old (37.10 ± 3.64 kg). Meloxicam concentration in plasma was determined by high-performance liquid chromatography and the data collected were evaluated by non-compartmental kinetic analysis. Meloxicam was detected in the plasma up to 72 h following i.v. administration in all age groups. The volume of distribution at steady state (Vdss ) and total body clearance (ClT ) were significantly higher in 1-month-old (304.87 mL/kg and 16.57 mL/h/kg) than in 12-month-old (193.43 mL/kg and 10.50 mL/h/kg) sheep. The area under the concentration-time curve from 0 to 72 h value of meloxicam was lower in 1-month-old (58.51 h*μg/mL) compared to 12-month-old (92.59 h*μg/mL) sheep. There was no difference in t1/2ʎz value in different age groups. The body extraction ratio values for meloxicam ranged from 0.0186 to 0.0719 after i.v. administration in all age groups. Meloxicam showed an increase in plasma concentration and a decrease in Vdss and ClT in 12-month-old compared to 1-month-old sheep. Compared to 1-month-old and 12-month-old sheep, there was no difference in these parameters in 6-month-old sheep. Because the age of sheep has an influence on the pharmacokinetics of meloxicam, dosage apparently may need to be adjusted for age.

EXTRACTION-FREE SPECTROPHOTOMETRIC DETERMINATION OF MELOXICAM USING BROMOTHYMOL BLUE

Objective: The purpose of the present work was to develop and validate a fast, simple and sensitive extraction-free spectrophotometric technique for the quantitative determination of meloxicam based on the reaction with bromothymol blue. Material and Method: The reference standard of meloxicam, bromothymol blue and finished dosage forms of meloxicam were used in the study. Absorption measurements were performed on the Analytic Jena UV-visible spectrophotometer model Specord 200. Result and Discussion: The developed method is based on the formation of the colored reaction product between meloxicam and bromothymol blue in acetone medium with absorption maximum at 348 nm. The method meets the requirements of the State Pharmacopoeia of Ukraine for such validation characteristics as specificity, linearity, precision, accuracy, robustness and range of application. The obedience to Beer's law is observed in the range of meloxicam concentrations 0.80-2.40 mg/100 ml, the correlation coefficient is 0.9998. The range of application of the method is 60-140%.

176 Evaluation of Meloxicam Plasma Concentrations Using a Microneedle Patch for Drug Delivery

Abstract To evaluate meloxicam plasma concentrations using a microneedle patch, 12 pigs (initial BW = 2.5 ± 0.53 kg) were stratified into of 4 treatment groups. Treatment groups were: 1) pigs (n = 2) received 0.5 mg/kg meloxicam via oral drench (oral); 2) pigs (n = 2) received a patch with no meloxicam (placebo); 3) pigs (n = 4) received microneedle patch dosed at 2.5 mg/kg (low dose); and 4) pigs (n = 4) received 2 microneedle patches dosed at 5 mg/kg (high dose). Blood was collected for plasma analysis at 0, 2, 4, 8, 12, 24, 48, 72, 96, and 168 hours. Microneedle patches were adhered on the pinna of the ear after blood collection at 0 hour. Statistical analyses were performed using the MIXED procedure of SAS 9.4, assessing effects of treatment, time, and treatment × time interaction. Statistical significance was determined at P ≤ 0.05, with tendencies at 0.05 &amp;lt; P ≥ 0.1. There was a treatment × time interaction (P &amp;lt; 0.0001), with the oral treatment group having greater meloxicam plasma concentrations at 2, 4, and 8 hours than placebo, low dose, and high dose treatment groups (P &amp;lt; 0.0001), but there were no differences for 24, 48, 72, 96, and 168 hours (P &amp;gt; 0.1). The oral treatment group tended to have greater meloxicam plasma concentrations at 12 hours compared with placebo (P = 0.09), low dose (P = 0.054), and high dose (P = 0.054) treatment groups. There were no differences between placebo, low dose, and high dose treatment groups for any blood collection timepoint (P &amp;gt; 0.1). Meloxicam concentrations in plasma were detectable but low for both the low dose treatment group (0.21 ng/mL) and high dose treatment group (1.14 ng/mL). Research is continuing to determine the ideal meloxicam dosage needed on the patch to deliver desired plasma concentrations.

Egg residue and depletion of meloxicam in Jing Hong laying hens following multiple oral doses

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) commonly used in an extra-label manner in commercial laying hens for the treatment of foot lesions, which are a common issue in this species. The present study aimed to determine the depletion profiles of meloxicam in eggs with multiple oral administration under 2 different dosing regimens and to further recommend reasonable withdrawal intervals (WDIs). Meloxicam (1 mg/kg) was administered orally to laying hens under 2 dosing schedules: 10 doses at 24-h intervals and 15 doses at 12-h intervals. Eggs were collected daily after the first dosing, and meloxicam concentrations in both yolk and white were determined by a high-performance liquid chromatography (HPLC) method. The weight ratio of white to yolk in the whole egg was 1.54 (the mean of 20 eggs with repeated tests), and this value combined with the meloxicam concentrations in white and yolk were used to calculate the drug concentrations in whole eggs. Meloxicam was quickly eliminated from egg white, and its concentrations could only be quantified at 2 time points during the elimination phase. The elimination half-lives in yolk and whole egg were 3.07 ± 1.00 and 2.98 ± 0.88 d, respectively, after 10 repeated doses. And the corresponding elimination half-lives were 2.30 ± 0.83 and 2.18 ± 0.67 d, respectively, after repeated 15 doses. Considering the time when meloxicam was not detectable in eggs with the time of ovum development and maturation, a withdrawal interval (WDI) was suggested as 17 d for both dosing schedules. The current results enriched the study on the residue of meloxicam in domestic Jing Hong laying hens and provided WDIs to help ensure animal-derived food safety.

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.

PHARMACOKINETICS OF MELOXICAM AFTER SINGLE ORAL AND INTRAMUSCULAR ADMINISTRATION IN CHINA ROCKFISH (SEBASTES NEBULOSUS).

Fish species are important for various purposes including aquaculture stock and display animals, but there are significant gaps in the medical knowledge regarding pharmacological parameters and effective pain management. Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that has been studied in few teleost species and with several administration routes. However, these species were typically freshwater or euryhaline fish, and evaluation in marine species is lacking. The pharmacokinetic properties of meloxicam were determined in nine adult China rockfish (Sebastes nebulosus), presumed healthy based on physical examination and benign medical histories. Based on a pilot study, China rockfish were given 1 mg/kg meloxicam via IM injection in the epaxial musculature, and, after a 48-h washout period, 1 mg/kg meloxicam was given by PO gavage. Blood samples were collected from the caudal vein at baseline and at nine time intervals over a 48-h time period following administration of meloxicam. Plasma meloxicam concentrations were determined by reverse phase high-performance liquid chromatography, and noncompartmental analysis was performed. The mean peak plasma concentration after IM injection was 4.9 µg/ml, and the mean terminal half-life was 5.0 h. The mean peak plasma concentration after PO administration was 0.07 µg/ml. Based on these findings, IM injected meloxicam reaches plasma levels consistent with therapeutic concentrations in select mammals, and peak levels were maintained for ≤12 h. Single-dose PO administration failed to achieve similar concentrations, and clinical practicality is unknown. Further studies evaluating NSAID multidose regimes and their pharmacodynamic effects may provide additional dosing information.

Meloxicam Performances for Copper Corrosion Inhibition in 1M HNO3: Experimental and Theoretical Approaches

Background: Copper is a metal that is widely used in many fields such as industry and construction, etc. These different industrial sectors use acid solutions such as nitric acid and hydrochloric acid, etc. The use of acid solutions in the industrial environment causes degradation of materials. In recent decades, the use of corrosion inhibitors has become very essential. Objective: The objective of our study is to test the performance of meloxicam as a copper corrosion inhibitor in a nitric acid medium. Methods: The studies were conducted using the gravimetric method and density functional theory (DFT) at B3LYP/6-311G (d, p) level of theory. The inhibitory efficiency of the molecule increases with increasing concentration of Meloxicam, but decreases with increasing temperature. The adsorption of the molecule on the copper surface follows the Villamil model. Results: The thermodynamic quantities of adsorption and activation were determined and discussed. Quantum chemical calculations have allowed determining the molecular descriptors. Conclusion: There is a good agreement between the experimental and theoretical results. Electrochemical studies are envisaged.

Evaluation of the Efficiency of a Soft Dosage Form for the Treatment of Osteoarthritis: Influence on the Level of Pro-inflammatory Cytokines

Introduction. Osteoarthritis is now considered to be a slowly progressive inflammatory disease that completely affects the joint. An important role in the development of this pathology is played by inflammation of the synovial membrane and ligaments (synovitis), supplemented by constant mechanical stress. Normally, a balance of anti-inflammatory and pro-inflammatory mediators is observed in cartilage, however, under the influence of risk factors, this balance shifts towards the latter.Aim. Evaluation of the effect of a previously developed soft dosage form containing meloxicam, a purine derivative and an immunomodulator M on the level of pro-inflammatory cytokines: IL-1α, IL-1β, IL-6 and TNF-α in osteoarthritis.Materials and methods. The experiment included 25 animals, which were divided into 5 groups by simple randomization: 1 – test (gel 0.5 %), 2 –test (gel 1 %), 3 – reference (Amelotex®, gel 1 %), 4 – control (gel base); 5 – intact. Preclinical modeling of the pathology was carried out by combined injection of 0.1 ml of a mixture of complete Freund's adjuvant with a 10 % suspension of talc in isotonic sodium chloride solution in a ratio of 1 : 10 into the cavity of the hock (tarsal) joint of Brown Norvay Catholic Rats male rats. Enzyme immunoassay of animal blood serum on the 28th day of the experiment was performed using standard ELISA plate kits (Cloud-Clone Corp., USA). Statistical data processing was performed using GraphPad Prism 8.0.2 software (GraphPad Software Inc., USA), differences were considered statistically significant at p &lt; 0.05.Results and discussion. The developed compositions contributed to a decrease in the level of pro-inflammatory cytokines (IL-1α, IL-6 and TNF-α) compared with the main and reference gel preparation. At the same time, differences were found between the effect observed from the use of the test agents (gel 0.5 %, gel 1 %) and the reference drug in terms of the effect on the level of IL-1α and TNF-α, which indicates a greater effectiveness of the selected combination of active substances, because, unlike the single-component gel Amelotex®, the compositions developed by us additionally included a purine derivative and an immunomodulator M. The data obtained are important from the point of view of understanding the mechanism of action of a soft dosage form.Conclusion. Based on the results of previous and present studies, it is assumed that the combined composition of the soft dosage form with a half (0.5 %) concentration of meloxicam is of greatest interest for clinical practice, since its use at a high level of effectiveness additionally reduces the likelihood of adverse reactions from the non-steroidal anti-inflammatory drug, which is important in the case of long-term therapy of osteoarthritis.

Osmotic pump maintains plasma concentrations of meloxicam for 6 days after orthopedic surgery in pigeons (Columba livia).

To determine the plasma concentration of meloxicam delivered via an osmotic pump in pigeons undergoing orthopedic surgery and if an osmotic pump is a suitable alternative to repeated oral administration of this drug. 16 free-ranging pigeons presented for rehabilitation with a wing fracture. An osmotic pump filled with 0.2 mL of 40 mg/mL meloxicam injectable solution was implanted subcutaneously in the inguinal fold of 9 pigeons under anesthesia for orthopedic surgery. The pumps were removed 7 days postsurgery. Blood samples were collected before pump implantation (time 0) and 3, 24, 72, and 168 hours after pump implantation in 2 pigeons in a pilot study then at 12, 24, 72, and 144 hours in the 7 pigeons of the main study. The blood of 7 other pigeons receiving meloxicam at 2 mg/kg, PO, every 12 hours was also sampled between 2 to 6 hours after the last meloxicam administration. Plasma meloxicam concentrations were measured via high-performance liquid chromatography. The plasma concentration of meloxicam was maintained at significant levels from 12 hours to 6 days after osmotic pump implantation. Median and minimum plasma concentrations in implanted pigeons were maintained at the same or higher level than those measured in pigeons that received meloxicam at a dose known to be analgesic in this species. No adverse effects attributable to either osmotic pump implantation and removal or meloxicam delivery were observed in this study. Plasma concentrations levels of meloxicam in pigeons implanted with osmotic pumps were maintained at a similar concentration or higher than the suggested analgesic meloxicam plasma concentration in this species. Thus, osmotic pumps could represent a suitable alternative to the frequent capture and handling of birds for analgesic drug administration.

Chitosan Encapsulated Meloxicam Nanoparticles for Sustained Drug Delivery Applications: Preparation, Characterization, and Pharmacokinetics in Wistar Rats

Meloxicam (MLX) is currently used in the therapeutic management of both acute and chronic inflammatory disorders such as pain, injuries, osteoarthritis, and rheumatoid arthritis in both humans and animals. Gastrointestinal toxicity and occasional renal toxicity were observed in patients taking it for a long-term period. Meloxicam's late attainment of peak plasma concentration results in a slow onset of action. The goal of the current study was to prepare and characterize chitosan encapsulated meloxicam nanoparticles (CEMNPs) with high bioavailability and less gastro intestinal toxicity in order to prevent such issues. The size of the prepared CEMNPs was approximately 110-220 nm with a zetapotential of +39.9 mV and polydispersity index of 0.268, suggesting that they were uniformly dispersed nanoparticles. The FTIR and UV-Vis spectroscopy have confirmed the presence of MLX in the prepared CEMNPs. The pharmacokinetics have been studied with three groups of male Wistar rats receiving either of the treatments, viz., 4 mg·kg-1 of MLX and 1 or 4 mg·kg-1 of CEMNPs. Plasma samples were collected until 48 h post administration, and concentrations of MLX were quantified by using reverse (C18) phase HPLC. Non-compartmental analysis was applied to determine pharmacokinetic variables. Upon oral administration, the maximum concentration (Cmax) was reached in 4 h for CEMNPs and 6 h for MLX. The mean area under the plasma MLX concentration-time curve from 'zero' to infinity (AUC0-∞), half-life (t1/2β), and mean resident time (MRT) of 1 mg·kg-1 of CEMNPs was 1.4-, 2-, and 1.8-fold greater than 4 mg·kg-1 of MLX. The prepared CEMNPs demonstrated quicker absorption and prolonged release along with a significant improvement in the bioavailability of MLX, paving a prospective path for the development of drugs with enhanced bioavailability with less side effects.