Plasma Concentrations Of Meloxicam Research Articles

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.

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.

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.

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 < P ≥ 0.1. There was a treatment × time interaction (P < 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 < 0.0001), but there were no differences for 24, 48, 72, 96, and 168 hours (P > 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 > 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.

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.

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.

Pharmacokinetics and bioavailability of meloxicam in rainbow trout (Oncorhynchus mykiss) broodstock following intravascular, intramuscular, and oral administrations.

The pharmacokinetics and bioavailability of meloxicam were investigated after single intravascular (IV), intramuscular (IM), and oral dose of 1mg/kg in rainbow trout broodstock at 11±1.2°C. A total of 36healthy rainbow trout (Oncorhynchus mykiss) broodstock weighing 1.40±0.26kg was used for the investigation. Plasma concentrations of meloxicam were measured with high-performance liquid chromatography-ultraviolet detection, and pharmacokinetic parameters were calculated by non-compartmental analysis. The elimination half-life for IV, IM, and oral routes was 3.63, 4.55, and 2.95h, respectively. The IV route for meloxicam showed the total clearance of 0.05 L/h/kg and volume of distribution at a steady state of 0.20L/kg. The peak plasma concentration was 2.97μg/ml for the IM route and 0.84μg/ml for the oral route. The bioavailability was 78.45% for the IM route and 21.48% for the oral route. Meloxicam following IM and oral administration displayed short t1/2ʎz . The short t1/2ʎz could be an advantage for the short-term use in acute conditions. The IM route with the good bioavailability can be preferred for the treatment of various conditions. However, developing new oral formulations with the good bioavailability for meloxicam is necessary to minimize stress and trauma through minimal handling in rainbow trout broodstock.

Comparative pharmacokinetics of meloxicam oil suspension in pigs at different dosages following intramuscular administration

This study aimed to evaluate the preliminary safety of self-developed meloxicam (MEL) oil suspension and determine the comparative pharmacokinetics of it at 0.8 and 2mg/kg body weight (b.w.) dosages in pigs following a single intramuscular administration. Six rabbits were used for the study of preliminary safety and six healthy pigs were used for pharmacokinetics study by a crossover design in two periods. The muscle irritation results showed that both of the MEL oil suspension and the conventional injection had no significant changes at the dosage of 0.4 mg/kg b.w.. However, at the dosage of 2 mg/kg b.w., both of the self-developed MEL oil suspension and the MEL conventional injection showed mild irritation to muscle. Plasma concentrations of MEL were measured by ultra performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The MEL plasma concentrations were quantified up to 30 h and 72 h after intramuscular administration at the low- and high-dosage, respectively. The difference was statistically significant (P < 0.05) between different dosages in pharmacokinetic parameters of t1/2λz, Cmax, AUC0-t, AUC0-μ, MRT, and Vd. The Cmax values of MEL were 1.92 ± 0.34 μg/ml and 3.03 ± 1.25 μg/ml at dosages of 0.8 and 2 mg/kg b.w. while the tmax values were 3.25 ± 1.04 h and 4.00 ± 1.26 h, respectively. The pharmacokinetics results of self-developed MEL oil suspension demonstrated that the retention time of it in pigs was prolonged, showing the sustained-release effect. Therefore, Oil suspension was an ideal new drug loading form of MEL.

Pharmacokinetics of meloxicam, carprofen, and tolfenamic acid after intramuscular and oral administration in Japanese quails (Coturnix coturnix japonica).

The aim of this study was to determine the pharmacokinetics of meloxicam (MLX), carprofen (CRP), and tolfenamic acid (TA) in Japanese quails (Coturnix coturnix japonica) following intramuscular (IM) and oral administration at doses of 1, 10, and 2mg/kg, respectively. A total of 72 quails were randomly divided into 3 equal groups as MLX, CRP, and TA. Each group was separated into two sub-groups that received IM and oral administration of each drug. Plasma concentrations of MLX, CRP, and TA were determined using HPLC-UV and analyzed by non-compartmental method. The t1/2ʎz and MRT of MLX, CRP, and TA after oral administration were similar to those after IM administration. The Vdarea /F of MLX, CRP, and TA after IM administration was 0.28, 2.05, and 0.20 L/kg. The Cl/F of MLX, CRP, and TA after IM administration was 0.12, 0.19, and 0.09 L/h/kg. MLX, CRP, and TA after oral administration showed significantly lower Cmax and longer Tmax compared with IM administration. The relative bioavailability of MLX, CRP, and TA following oral administration in quails was 76.13%, 61.46%, and 57.32%, respectively. The IM and oral route of MLX, CRP, and TA can be used for the treatment of various conditions in quails. However, further research is necessary to determine the pharmacodynamics and safety of MLX, CRP, and TA before use in quails.

Role of eprinomectin as inhibitor of the ruminant ABCG2 transporter: Effects on plasma distribution of danofloxacin and meloxicam in sheep

Therapeutic outcome results of the coadministration of several drugs in veterinary medicine is affected by, among others, the relationship between drugs and ATP-binding cassette (ABC) transporters, such as ABCG2. ABCG2 is an efflux protein involved in the bioavailability and milk secretion of drugs. The aim of this work was to determine the role of eprinomectin, a macrocyclic lactone (ML) member of avermectin class, as inhibitor of ABCG2. The experiments were carried out through in vitro inhibition assays based on mitoxantrone accumulation and transport assays in ovine ABCG2 transduced cells using the antimicrobial drug danofloxacin and the anti-inflammatory drug meloxicam, both widely used in veterinary medicine and well known ABCG2 substrates.The inhibition results obtained showed that eprinomectin was an efficient in vitro ABCG2 inhibitor, tested in mitoxantrone accumulation assays. In addition, this ML decreased ovine ABCG2-mediated transport of danofloxacin and meloxicam. To evaluate the role of eprinomectin in systemic exposure of drugs, pharmacokinetic assays based on subcutaneous coadministration of eprinomectin with danofloxacin (1.25 mg/kg) or meloxicam (0.5 mg/kg) in sheep were performed obtaining a significant increase of systemic exposure of these drugs. Especially relevant was the increase of the systemic concentration of meloxicam, since coadministration with eprinomectin increased significantly the plasma concentration of meloxicam, obtaining an increase of AUC (0–72 h) value of more than 40%.

Pharmacokinetics of Sustained-release, Oral, and Subcutaneous Meloxicam over 72 Hours in Male Beagle Dogs.

In cynomolgus macaques, plasma levels of sustained-release formulations of meloxicam meet or exceed efficacious concentrations for 48 to 72 h, thereby allowing less animal handling and providing more consistent efficacy than standard formulations of meloxicam. The goal of this study was to compare the pharmacokinetics of a single subcutaneous dose of a sustained-release formulation of meloxicam (Melox-SR) with those of oral (Melox-PO) and standard subcutaneous (Melox-SC) formulations dosed every 24 h for 3 consecutive days. Dogs (5 or 6 adult male Beagles) each received the following 3 treat- ments: first, Melox-SR (10 mg/mL, 0.6 mg/kg SC once), next Melox-SC (0.2 mg/kg SC once, followed by 0.1 mg/kg SC every 24 h), and finally Melox-PO (same dosage as Melox-SC), with a washout period of at least 2 wk between formulations. Blood was collected at 0 (baseline), 1, 4, 8, 12, 24, 48, and 72 h after the initial administration of each formulation for comparison of meloxicam plasma concentrations. Blood was also collected before administration and at 48 h after Melox-SR injection for CBC and chemistry analysis. Plasma concentrations (mean ± 1 SD) of Melox-SR peaked at the 1-h time point (2180 ± 359 ng/ mL), whereas those of Melox-PO (295 ± 55 ng/mL) and Melox-SC (551 ± 112 ng/mL) peaked at the 4-h time point. Melox-SR yielded significantly higher plasma concentrations than Melox-PO and Melox-SC until the 48 and 72-h time points, respec- tively. Melox-SC plasma concentrations were significantly higher than those of Melox-PO at 4, 8, 12, 24, 48 and 72 h. No lesions were noted at the Melox-SR injection sites, and Melox-SR administration was not associated with changes in the CBC and serum chemistry panels. A single 0.6-mg/kg dose of Melox-SR can yield plasma concentrations that exceed 350 ng/mL for at least 72 h in adult male dogs.

Pharmacokinetics and relative bioavailability of meloxicam oil suspension in pigs after intramuscular administration.

This study aimed to develop one novel meloxicam (MEL) oil suspension for sustained-release and compare the pharmacokinetic characteristics of it with MEL conventional formulation in pigs after a single intramuscular administration. Six healthy pigs were used for the study by a crossover design in two periods with a withdrawal interval of 14days. Plasma concentrations of MEL were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetic parameters were calculated by noncompartmental methods. The difference was statistically significant (p<.05) between MEL oil suspension and MEL conventional formulation in pharmacokinetic parameters of mean residence time (6.16±4.04)hr versus (2.66±0.55)hr, peak plasma concentration (Cmax ) (0.82±0.12)µg/ml versus (1.12±0.22) µg/ml, time needed to reach Cmax (Tmax ) (2.33±0.82)hr versus (0.59±0.18)hr, and terminal elimination half-life (t1/2λz ) (3.74±2.66)hr versus (1.55±0.37)hr. The mean area under the concentration-time curve (AUC0-∝ ) of MEL oil suspension and MEL conventional formulation was 5.35 and 3.43hrµg/ml, respectively, with a relative bioavailability of 155.98%. Results of the present study demonstrated that the MEL oil suspension could prolong the effective time of drugs in blood, thereby reducing the frequency of administration on a course of treatment. Therefore, the novel MEL oil suspension seems to be of great value in veterinary clinical application.

Plasma pharmacokinetic profile and efficacy of meloxicam administered subcutaneously and intramuscularly to sheep.

Plasma pharmacokinetic profiles and the anti-inflammatory efficacy of meloxicam were determined when administered subcutaneously (SC) or intramuscularly (IM) to sheep. Merino ewes were initially injected with 0.1 mL of oil of turpentine into a forelimb to induce inflammation, followed by either 1.0 mg/kg or 2.0 mg/kg of meloxicam administered either SC or IM (n = 6 per treatment group) or followed by no meloxicam administration (control) (n = 4). Ewes were examined to determine skin temperature, limb circumference, limb sensitivity and signs of lameness at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 48 h following treatment, with blood collected at these time-points to quantify meloxicam plasma concentrations. Skin temperature of ewes dosed with meloxicam at 1.0 mg/kg SC and 2.0 mg/kg IM at 12 h and 1.0 mg/kg SC at 24 were significantly different to the controls (P < 0.05). Limb circumferences of ewes dosed with 1.0 mg/kg IM were significantly different to controls at 10 h and 12 h (P < 0.05). All meloxicam treatment groups resulted in reduced limb sensitivity compared to controls at 6 h, with the 1.0 and 2.0 mg/kg IM treatments significantly different at 12 h (P < 0.05) and 1.0 and 2.0 mg/kg SC groups, significantly different to controls at 48 h (P < 0.05). No significant difference in lameness scores were detected over 48 h. The 1.0 mg/kg IM treatment had a significantly greater plasma meloxicam concentration than the 1.0 mg/kg SC treatment over 0.5 to 4 h (P < 0.001). Both 1.0 mg/kg SC and IM treatments demonstrated elimination half-lives (mean ± SD) of 10.82 ± 2.46 and 12.63 ± 2.37 h, respectively. Meloxicam at all doses provided some anti-inflammatory and analgesic effects from 6 to 48 h; however no route could be distinguished as more efficacious than the others.

Pharmacokinetics and absolute oral bioavailability of meloxicam in guinea pigs (Cavia porcellus)

ObjectiveTo investigate the pharmacokinetics and absolute oral bioavailability of meloxicam in guinea pigs. Study designProspective crossover study. AnimalsA group of six healthy male Dunkin Hartley guinea pigs. MethodsA single dose of meloxicam (1.5 mg kg−1) was administered orally and intravenously (IV) to six healthy male guinea pigs. A wash-out period of 48 hours was taken into account between administrations (oral and IV) in the same animal. Blood was sampled through a central venous catheter before administration (t = 0 hours) and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 and 28 hours post administration. After centrifugation, plasma concentrations of meloxicam were measured by high-performance liquid chromatography with UV detection, and pharmacokinetic parameters were calculated using noncompartmental analysis. ResultsMeloxicam in guinea pigs exhibited a moderate absorption rate after oral dosing (time to maximal plasma concentration 3.7 ± 1.7 hours) and maximal plasma concentration was 0.92 ± 0.30 μg mL−1. After IV administration, total body clearance and volume of distribution were 0.13 ± 0.04 and 0.72 ± 0.36 L kg−1, respectively. Terminal half-life was 3.7 ± 0.7 hours and 3.5 ± 1.1 hours after IV and oral administration, respectively. Body extraction ratio was 0.0087 and mean absorption time was 3.8 ± 1.7 hours. The absolute oral bioavailability was 0.54 ± 0.14 in unfasted guinea pigs. Conclusions and clinical relevanceThis study reported the pharmacokinetics of meloxicam in guinea pigs. Studies concerning efficacy and safety are the next step towards a rational use of this drug in guinea pigs.

Pharmacokinetics of meloxicam during multiple oral or intramuscular dose administration to African grey parrots (Psittacus erithacus).

OBJECTIVE To determine the pharmacokinetics of meloxicam in African grey parrots (Psittacus erithacus) during administration of multiple doses. ANIMALS 6 healthy African grey parrots. PROCEDURES Meloxicam was administered at each of 3 dosages (1 mg/kg, IM, q 24 h, for 7 days; 1 mg/kg, PO, q 24 h, for 12 days; and 1.6 mg/kg, PO, q 24 h, for 7 days) with an 8-week washout period between treatments. Blood samples were collected 12 and 24 hours after each drug administration (times of presumptive peak and trough drug concentrations) for pharmacokinetic analysis. Birds were visually assessed during all experiments and monitored for changes in selected plasma and urine biochemical variables after administration of the drug at 1.6 mg/kg. RESULTS Mean trough plasma concentrations at steady state were 10.7 and 9.16 μg/mL after meloxicam administration at 1 mg/kg, IM, and 1 mg/kg, PO, respectively. Plasma drug accumulation was evident (accumulation ratios of 2.04 ± 0.30 [IM treatment] and 2.45 ± 0.26 [PO treatment]). Plasma and urine N-acetyl-β-d-glucosaminidase activities were significantly increased at the end of meloxicam treatment at 1.6 mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE Plasma concentrations of meloxicam were maintained at values greater than effective analgesic concentrations described for other avian species. Although administration of meloxicam at a dosage of 1 mg/kg IM and PO daily for 1 week and 12 days, respectively, was not associated with adverse clinical effects in this population, further studies are needed to assess the efficacy and safety of the drug during prolonged treatment and the clinical relevance of its accumulation.

Plasma Concentrations of Ketoprofen and Meloxicam after Subcutaneous and Topical Administration in the Smoky Jungle Frog (Leptodactylus pentadactylus)

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for analgesia in veterinary patients; however, evaluation of NSAID pharmacokinetics in amphibians is limited. A wide variety of pharmacotherapeutics have been administered topically to the skin of anurans with limited empirical evidence of absorption or efficacy. Systemic absorptions of two NSAIDs, meloxicam and ketoprofen, were evaluated after subcutaneous and topical cutaneous administration in smoky jungle frogs (Leptodactylus pentadactylus). Eighty-four, 8 month old, 38.0 g (26.1–56.6 g) (median [range]) frogs were randomly assigned to receive one of four treatments, with 21 animals in each group: 1 mg/kg racemic ketoprofen administered either subcutaneously (SK) or topically (TK) or 0.2 mg/kg meloxicam administered either subcutaneously or topically. Plasma concentrations of meloxicam and the R- and S-enantiomers of ketoprofen were quantified at 3, 8, and 24 h after administration. At each time point, seven frogs per group were anesthetized for blood collection and then euthanized. Plasma samples were pooled within each group for drug quantification. Both enantiomers of ketoprofen were detectable in groups SK and TK, and plasma concentrations decreased from 3 to 24 h. The drop in concentration was less predictable for TK than for SK. Plasma concentrations of meloxicam were nondetectable at most time points by both routes. Topical absorption of ketoprofen is possible in frogs, although therapeutic levels have not been determined for this species.

Pharmacokinetic properties of low-dose SoluMatrix meloxicam in healthy adults.

SoluMatrix® meloxicam has been developed using SoluMatrix Fine Particle Technology™ to produce a meloxicam drug product with enhanced absorption properties to enable treatment at lower doses than available oral meloxicam drug products. This follows recognition of serious dose-dependent adverse events (AEs) associated with nonsteroidal anti-inflammatory drugs, including meloxicam. This study investigated the pharmacokinetic (PK) properties of SoluMatrix meloxicam 5-mg (fasting conditions) and 10-mg capsules (fasting and fed conditions) and compared SoluMatrix meloxicam 10-mg capsules with meloxicam 15-mg tablets under fasting conditions. This four-period crossover study randomized 28 healthy adult participants to receive single doses of SoluMatrix meloxicam 5-mg capsules (fasting) and 10-mg capsules (fasting or fed) and meloxicam tablets 15mg (fasting). Meloxicam plasma concentrations were assessed through 96h postdose. Safety was assessed. Twenty-five participants (89.3%) completed the study. Under fasting conditions, SoluMatrix meloxicam 10mg [1252.8 (254.22) ng/mL] produced similar meloxicam mean (standard deviation (SD)) maximum plasma concentrations vs meloxicam 15-mg tablets [1288.8 (424.40) ng/mL]. The overall mean (SD) systemic meloxicam exposure was 33% lower for SoluMatrix meloxicam 10mg [29,173.01 (11,042.09) ng*h/mL] vs meloxicam 15-mg tablets [40,875.6 (11,733.47) ng*h/mL]. The median time to maximum plasma meloxicam levels occurred earlier following SoluMatrix meloxicam 5mg (2.0h) and 10mg (2.0h) administration vs meloxicam 15-mg tablets (4.0h). Few study-medication-related AEs were reported. SoluMatrix meloxicam 10mg was more rapidly absorbed and associated with a lower overall exposure compared with meloxicam 15-mg tablets in this study in healthy adults under fasting conditions.

Pharmacokinetic profiles of meloxicam in turtles (Trachemys scripta scripta) after single oral, intracoelomic and intramuscular administrations.

Meloxicam is an anti-inflammatory and analgesic drug used to treat many pathological conditions in turtles. With the aim to fill the lack of data about its pharmacokinetic in this species, eighteen turtles (Trachemys scripta scripta) were divided in three groups and treated with a single dose of meloxicam (0.2 mg/kg) by intramuscular, intracoelomic and oral route, respectively. At scheduled time points, blood samples were collected and meloxicam concentrations were determined by HPLC. Pharmacokinetic parameters were calculated from the obtained concentration-time curves. After intramuscular treatment, a plasma peak of meloxicam equal to 1590.03 ± 1845.32 ng/mL (mean ± SD) and a Tmax of 1.17 ± 0.45 h were reached, indicating a quick absorption of the drug. The intracoelomic administration brought to the largest AUC (12621.04 ± 6203.79 h*ng/mL) and to a Cmax and a Tmax equal to 1154.52 ± 662.78 ng/mL and 2.82 ± 1.39 h, respectively. Following oral treatment, the plasma concentrations of meloxicam were very low indicating a scarce absorption. Further studies are warranted to determine the effective plasma concentration of meloxicam in turtles and, consequently, the dosage regimen.

Pharmacokinetic behavior of meloxicam in loggerhead sea turtles (Caretta caretta) after intramuscular and intravenous administration.

Data on reptile analgesia are scarce for nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids and almost completely lacking in sea turtles, even though emergencies requiring correct pain management are very frequent in their rehabilitative medicine; therefore, dosage regimens extrapolated from other species involve the risk of clinical failure and damage to the animals. We describe the pharmacokinetic behavior of meloxicam in the loggerhead sea turtle (Caretta caretta). We chose meloxicam because of its selective anti-cyclooxygenase-2 activity and lesser adverse side effects. No data are available on the capacity of turtles to tolerate NSAIDs, so we chose a dose of 0.1 mg/kg of meloxicam. Plasma concentrations of meloxicam were unexpectedly low both for intravenous (IV; maximum concentration [C(max)] = 0.04±0.02 µg/mL) and intramuscular (IM; C(max) = 0.07±0.09 µg/mL) administration. A double-peak phenomenon occurred after both IV (time for second peak concentration T(max2) = 10.33±10.89 h) and IM (T(max2) = 1.17±0.75 h). The second peak after IM injection was premature, so some difficulty and delay in absorption appears to be an appropriate explanation. Furthermore, the area under the curve, and therefore systemic bioavailability (F = 31.82±28.24%), after both IV (0.30±0.29) and IM (0.10±0.03) injection appeared particularly limited. Terminal elimination slope and mean residence time indicated fast elimination after IM dosing; as a consequence, plasma concentrations dropped below analytic limits in 8 h. Considering that IM is the favored route of administration of drugs in rescue centers, it is unlikely that meloxicam at 0.1 mg/kg is an appropriate choice, particularly in long-term pain management protocols.

Comparative Disposition Kinetics of Meloxicam Following a Single Intravenous Bolus Dose and Its Concurrent Administration with Ofloxacin in Yak and Cattle

Present study describes the comparative pharmacokinetic (PK) profile of meloxicam (0.5 mg.kg-1) alone its concurrent administration with ofloxacin (7.5 mg.kg-1) by intravenous route in yak and cattle. Plasma concentration of meloxicam was determined by HPLC assay and pharmacokinetic parameters by compartmental method using “PHARMKIT” software. Following intravenous administration of meloxicam alone, t1/2α, t1/2β, AUC, Vdarea and ClB values were found to be 0.21+0.04 h, 4.65+0.40 h, 25.46+1.22 μg/ml.h, 1.97+0.11 L/kg and 0.35+0.02 L/h/kg, respectively in yak and all these values were almost comparable to those found in cattle. But the values of K12/K21, Vc, Vp and fc differed significantly between yak and cattle. Further, no significant differences were observed in values of majority of the pharmacokinetic parameters between meloxicam alone or its concurrent administration with ofloxacin in yak and cattle except the values of Vc, Vp and T/P which differed significantly between alone and concurrent administration in yak but not in cattle. Based on pharmacokinetic variables, the loading and maintenance doses of meloxicam were found to be 1.05 and 0.88 mg.kg-1 body weight for yak and 0.97 and 0.79 mg.kg-1 for cattle and be repeated at 12 h interval. Results of present study further suggest that important pharmacokinetic parameters do not significantly differ between yak and cattle and meloxicam can be used at same dose levels in both the species and adjustment in dosage regimen of meloxicam is not warranted in either of the species, if to be used concurrently with ofloxacin.