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1.
Repeated administration of meloxicam can cause kidney damage in cats by mechanisms that remain unclear. Metabolomics and lipidomics are powerful, noninvasive approaches used to investigate tissue response to drug exposure. Thus, the objective of this study was to assess the effects of meloxicam on the feline kidney using untargeted metabolomics and lipidomics approaches. Female young‐adult purpose‐breed cats were allocated into the control (n = 4) and meloxicam (n = 4) groups. Cats in the control and meloxicam groups were treated daily with saline and meloxicam at 0.3 mg/kg subcutaneously for 17 days, respectively. Renal cortices and medullas were collected at the end of the treatment period. Random forest and metabolic pathway analyses were used to identify metabolites that discriminate meloxicam‐treated from saline‐treated cats and to identify disturbed metabolic pathways in renal tissue. Our results revealed that the repeated administration of meloxicam to cats altered the kidney metabolome and lipidome and suggest that at least 40 metabolic pathways were altered in the renal cortex and medulla. These metabolic pathways included lipid, amino acid, carbohydrate, nucleotide and energy metabolisms, and metabolism of cofactors and vitamins. This is the first study using a pharmacometabonomics approach for studying the molecular effects of meloxicam on feline kidneys.  相似文献   

2.
The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high‐performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss) of 0.22 ± 0.12 L/kg. Median plasma terminal half‐life (t1/2) was 1.19 h (range 0.71–1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (Cmax 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4–8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5‐hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate.  相似文献   

3.
The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297–392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 μg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC–MS–MS methods. The mean (± SD) Cmax, Cmin, and Caverage plasma meloxicam concentrations were 4.52 ± 0.87 μg/mL, 2.95 ± 0.77 μg/mL, and 3.84 ± 0.81 μg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam‐treated calves will have low residue concentrations by 21 days after repeated oral administration.  相似文献   

4.
Grudé, P., Guittard, J., Garcia, C., Daoulas, I., Thoulon, F., Ebner, T. Excretion mass balance evaluation, metabolite profile analysis and metabolite identification in plasma and excreta after oral administration of [14C]‐meloxicam to the male cat: preliminary study. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2010.01157.x. The objective of this study was to investigate the metabolic pathways and routes of excretion of oral meloxicam in the cat. [14C]‐meloxicam was administered orally to three fasted male cats. Urine, faeces, vomit and cage washes were collected over the following 144 h period. Blood was collected predosing and at 3 and 12 h postdosing. Metabolites were identified by HPLC/MS/MS. When possible a metabolic structure was proposed for each metabolite detected. Only unchanged meloxicam was identified in plasma. Five major metabolites were detected in urine and four in faeces, which were identified by HPLC/MS/MS as products of oxidative metabolism. No conjugated metabolites were detected. Elimination occurred early (61% during the first 48 h). A total of 21% of the recovered dose was eliminated in urine (2% as unchanged meloxicam, 19% as metabolites) and 79% in the faeces (49% as unchanged meloxicam, 30% as metabolites). The results indicate that after oral administration the major route of excretion of meloxicam in the cat is faecal and that the main pathway of biotransformation of meloxicam in the cat is oxidation.  相似文献   

5.
Mycophenolic acid (MPA) has been shown to be promising for the treatment of autoimmune diseases in dogs and cats. In humans, MPA is highly bound to plasma proteins (~97%). It has been recommended to monitor free drug plasma concentrations because the free MPA correlates with its immunosuppressive effect. However, it is unknown if MPA is highly bound to plasma proteins in dogs and cats. The objectives of this study were to determine the extent of plasma protein binding of MPA and evaluate the effect of prednisolone and dexamethasone on the extent of protein binding of MPA in dogs and cats. The extent of plasma protein binding of MPA was determined in plasma collected from clinically healthy adult cats (n = 13) and dogs (n = 14) by combining high‐throughput dialysis and ultra‐high‐liquid chromatography. This study reveals that MPA is highly bound to plasma proteins (>90%) in dogs and cats, mean extent of binding of MPA at 15 μg/ml to plasma proteins being 96% (range, 95%–97%) and 92% (range, 90%–93%) for dogs and cats, respectively. In dog plasma, MPA is primarily bound to albumin. In vitro, prednisolone increased the unbound MPA in dogs (p < .01) but not in cats (p = .07) while dexamethasone had no effect on MPA plasma binding in either species (p > .05). Results of this study provide valuable information for designing future pharmacokinetic and pharmacodynamic studies and also therapeutic monitoring programs for dogs and cats.  相似文献   

6.
ObjectiveTo compare the effects of meloxicam or carprofen on glomerular filtration rate (GFR), and to evaluate the effect of meloxicam on urinary N-acetyl-β-D-glucosaminidase (NAG) activity, of cats after dental surgery.Study designRandomized, blinded, controlled trial.AnimalsA total of 24 mixed breed cats.MethodsCats were randomly assigned to one of three groups (n = 8 per group): meloxicam (0.2 mg kg–1); carprofen (4 mg kg–1); or saline (2 mL). Acepromazine (0.04 mg kg–1) and buprenorphine (0.02 mg kg–1) were administered intramuscularly as preanaesthetic medication. Test drugs were injected subcutaneously at the time of preanaesthetic medication. Anaesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. Mean arterial blood pressure (MAP), respiratory rate (fR), heart rate (HR) and haemoglobin oxygen saturation values (SpO2) were recorded. All cats underwent ultrasonic dental scaling with polishing. Teeth extraction involved mucosal flap creation, removal of alveolar bone and flap closure. Plasma iohexol clearance (ICL), a measure of GFR, was estimated before and 24 hours after anaesthesia induction in all cats. Urinary NAG index was estimated in saline and meloxicam groups at the same time points as GFR. Between-group and -time point differences in GFR and NAG index were compared using mixed model analyses. Data are presented as mean ± standard deviation (p < 0.05).ResultsThere was no significant difference in plasma ICL rate (range: from 1.22 ± 0.05 to 1.27 ± 0.04 mL kg minute–1) between groups or between time points. Urinary NAG index (range: from 1.0 ± 0.19 to 1.36 ± 0.29 Units gram–1) was not significantly different between meloxicam and saline groups. MAP, HR, fR and SpO2 did not differ significantly between groups.Conclusions and clinical relevanceMeloxicam and carprofen appeared to produce nonsignificant effects on GFR, and meloxicam did not affect the urinary NAG activity, of cats after dental surgery.  相似文献   

7.
Approved analgesic compounds in cattle are not currently available in the United States due to the lack of validated pain assessment methods and marker residue depletion studies. In this study, we compared the pharmacokinetic parameters and effect of preemptive analgesics administered to calves subjected to dehorning with local anesthesia. Holstein steers were randomly assigned to receive one of the following treatments per os (PO) or intravenously (IV) (n = 8/group): meloxicam (1 mg/kg PO), gabapentin (15 mg/kg PO), meloxicam (1 mg/kg), and gabapentin (15 mg/kg) PO, flunixin (2.2 mg/kg IV), or a placebo. Plasma drug, haptoglobin, substance P (SP) concentrations, serum cortisol concentrations, ocular thermography, mechanical nociceptive threshold (MNT), and average daily gain (ADG) were evaluated. Data were analyzed using mixed‐effects models and noncompartmental pharmacokinetic analysis. Meloxicam, gabapentin, and meloxicam with gabapentin at the present doses did not reduce cortisol concentrations. Analgesic‐treated calves had significantly lower plasma SP concentrations and improved ADG compared with controls. Flunixin calves had reduced circulating cortisol compared with controls. Meloxicam‐treated calves showed an increase in MNT at two horn bud sites compared with the other treatments. Analgesics improved ADG and reduced biomarkers of pain, but effects differed by compound and route of administration.  相似文献   

8.
Grapiprant is the novel selective EP4 receptor inhibitor recently issued on the veterinary market for dogs affected by osteoarthritis. The aim of this study was twofold: to evaluate the pharmacokinetics and the pharmacodynamics of grapiprant in the induced inflammatory pain model in the rabbit after a single IV injection of 2 mg/kg; to compare the thermal antinociception effect after 2 mg/kg IV grapiprant, with that generated by 0.5 mg/kg meloxicam SC injected. Rabbits (n = 12) were randomly assigned to two crossover studies (single‐dose, two‐period crossover). The first study group A (n = 3) received a single IV dose of grapiprant at 2 mg/kg dissolved in ethanol. Group B (n = 3) received a single IV injection of ethanol (equivalent volume to grapiprant volume) at the same site. The second study group C (n = 3) received a single SC dose of meloxicam at 0.5 mg/kg. Group D (n = 3) received a single SC injection of 15% ethanol (equivalent volume to grapiprant volume) at the same site. After a 2‐week washout period, the groups were rotated and the experiments repeated. Blood samples (0.7 mL) were collected from the right ear artery at assigned times and grapiprant plasma concentrations determined by a validated HPLC‐FL method. Three hours prior to administration of the drugs, inflammation was induced by SC injection of lambda carrageenan (200 μL, 3% in physiological saline) under the plantar surface of the right hind paw. At a similar time to the blood collection, an infrared thermal stimuli (40 °C) was applied to the plantar surface of the rabbits’ hindlimbs to evaluate the thermal withdrawal latency (TWL). The thermal antinociceptive effect was expressed as maximum possible response (% MPR). Grapiprant plasma concentrations were detectable up to the 10‐h time point (concentration range 17–7495 ng/mL). The grapiprant‐treated group showed a significant increase in TWL from 1 h and up to 10 h after drug administration compared to the control. In contrast, the meloxicam group showed a significant increase in TWL from 4 up to 10 h after drug administration, compared to control. The maximal MPR% was not statistically different between the grapiprant and meloxicam group from 4 to 8 h, while significant differences were shown at 1, 1.5, 2, 10 and 24 h. Given these findings, grapiprant appears to be an attractive option for antinociception in rabbits, due to its rapid onset and extended duration of effect.  相似文献   

9.

Background

The pharmacokinetics, efficacy, and safety of meloxicam have been evaluated in adult horses, but not foals. Physiologic differences between neonates and adults might alter drug pharmacokinetics and therapeutic index.

Hypotheses

The pharmacokinetics of meloxicam will be different in foals compared with adult horses, and foals could be at increased risk for adverse drug effects.

Animals

Twenty lightbreed foals less than 6 weeks of age at commencement of the study.

Methods

Single and repeated oral dose pharmacokinetics were determined for meloxicam (0.6 mg/kg) in 10 foals. The safety of the drug was further evaluated in a 2nd group of 10 foals in a randomized blinded prospective study.

Results

Plasma concentrations after a single oral dose of meloxicam (0.6 mg/kg) and time to maximum plasma concentration were similar to adult horses. However, drug clearance was much more rapid in foals (elimination half‐life 2.48 ± 0.25 hours). Administration of 0.6 mg/kg every 12 hours was well tolerated by foals for up to 3 weeks, with no evidence of drug accumulation in plasma. Adverse effects observed in adult horses at higher dose rates were not observed in foals given 1.8 mg/kg twice daily for 7 days.

Conclusions and clinical importance

Meloxicam at an oral dose rate of 0.6 mg/kg every 12 hours provided plasma concentrations likely to be therapeutic. In contrast to findings for other NSAIDs, foals appeared more resilient to the adverse effects of this drug than was observed in adult horses.  相似文献   

10.
The objective of this study was to assess the pharmacokinetic profile and determine whether any adverse effects would occur in seven healthy adult horses following oral meloxicam tablet administration once daily for 14 days at a dose of 0.6 mg/kg·bwt. Horses were evaluated for health using physical examination, complete blood count, serum chemistry, urinalysis, and gastroscopy at the beginning and end of the study. Blood was collected for the quantification of meloxicam concentrations with liquid chromatography and mass spectrometry. The mean terminal half‐life was 4.99 ± 1.11 h. There was no significant difference between the mean Cmax, 1.58 ± 0.71 ng/mL at Tmax 3.48 ± 3.30 h on day 1, 2.07 ± 0.94 ng/mL at Tmax 1.24 ± 1.24 h on day 7, and 1.81 ± 0.76 ng/mL at 1.93 ± 1.30 h on day 14 (P = 0.30). There was a statistically significant difference between the Tmax on the sample days (P = 0.04). No statistically significant increase in gastric ulcer score or laboratory analytes was noted. Oral meloxicam tablets were absorbed in adult horses, and adverse effects were not statistically significant in this study. Further studies should evaluate the adverse effects and efficacy of meloxicam tablets in a larger population of horses before routine use can be recommended.  相似文献   

11.
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12.
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.  相似文献   

13.
The main objective of this study was to determine if administration of meloxicam, a cyclooxygenase (COX) two inhibitor, to heifers in which embryo transfer (ET) is more difficult and requires a greater manipulation of the tract, would be beneficial. Nulliparous recipient heifers were divided in two groups: CON (n = 102), in which animals received 10 ml of saline IM (the same volume of meloxicam) and MEL (n = 105) animals that were treated with meloxicam. According to the degree in passing the catheter, recipients from both groups were classified as Grade I, easy (< 60 s), and Grade II (more than 80 s), difficult. Immediately after embryo transfer, MEL recipients received an injection of 200 mg of meloxicam (10 ml).There was no difference in the pregnancy rates on Day 35 considering animals which presented Grade I cervix independently whether the treatment was performed or not (p = 0.22). There was a statistical difference in the pregnancy rates (p < 0.01) between both groups (49.0% and 66.7% for CON and MEL, respectively) when cervical grade was not considered, on Day 35. Considering the animals that presented Grade II cervix, the pregnancy rate was higher for MEL (21.15% and 78.84%, respectively) in both examinations (p < 0.01).The authors concluded that meloxicam had a positive influence on general pregnancy rate of treated heifers in comparison to non‐treated heifers. It was also observed that pregnancy rate was not influenced by meloxicam administration in Grade I heifers. Treatment increased the pregnancy rate of Grade II heifers.  相似文献   

14.
ObjectiveTo evaluate the cyclooxygenases (COX) inhibition, adverse effects and analgesic efficacy of dipyrone or meloxicam in cats undergoing elective ovariohysterectomy.Study designProspective, blinded, randomized, clinical study.AnimalsA total of 30 healthy young cats.MethodsThe cats were randomly assigned to three postoperative groups: D25 (dipyrone 25 mg kg?1 every 24 hours), D12.5 (dipyrone 12.5 mg kg?1 every 12 hours) and M (meloxicam 0.1 mg kg?1 every 24 hours). In the first 24 hours, the drugs were administered intravenously (IV), and then orally for 6 (dipyrone) or 3 days (meloxicam). Prostanoids thromboxane B2 and prostaglandin E2 concentrations served as indicators of COX activity and, with physiological variables and pain and sedation scores, were measured for 24 hours after first analgesic administration. Rescue analgesia (tramadol, 2 mg kg?1 IV) was provided if Glasgow feline composite measure pain scale (CMPS-Feline) ≥5. Laboratory tests included symmetric dimethylarginine and adverse effects were evaluated regularly up to 7 and 10 days after surgery, respectively. Parametric and nonparametric data were analyzed with two-way anova and Kruskal-Wallis tests, respectively (p < 0.05).ResultsIn the first half hour after analgesic administration, COX-1 activity was close to zero and remained significantly lower than before drug administration for 24 hours in all groups. The inhibition of COX-2 activity was significant for 30 minutes in all groups and up to 4 hours in group M. No alterations in laboratory tests or significant adverse effects were observed. Pain scores and need for rescue analgesia did not differ statistically among groups.ConclusionsDipyrone at both doses and meloxicam provided a nonselective inhibition of COX-1 and -2 activities and effective analgesia without causing significant adverse effects or laboratory tests alterations.Clinical relevanceDipyrone at both doses provides equally effective analgesia without causing adverse effects in cats undergoing ovariohysterectomy.  相似文献   

15.
Lehr, T., Narbe, R., Jöns, O., Kloft, C., Staab, A. Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats. J. vet. Pharmacol. Therap. 33 , 277–286. The objectives of these investigations were: first, to describe the pharmacokinetic properties of meloxicam in cats following single and multiple oral administration and secondly, to simulate different oral dosage regimes for meloxicam in cats after multiple dose administration to illustrate and evaluate those dosage regimes for the alleviation of inflammation and pain in cats. Six healthy domestic short hair cats were treated orally with various dosage regimes (0.05–0.2 mg/kg/day). Plasma samples were collected at predefined times and quantitatively analysed using liquid/liquid extraction followed by reverse phase HPLC with UV‐detection. Meloxicam plasma concentration data were analysed using the population pharmacokinetic approach (software: NONMEM). The final model was used to simulate different dosage regimes. The plasma concentration–time profiles of meloxicam in cats after oral single and multiple dose administration were best described by an open one‐compartment model with first‐order absorption and first‐order elimination. Pharmacokinetic parameters were estimated to be 0.00656 L/h/kg for the total apparent body clearance (CL/F), 0.245 L/kg for the apparent volume of distribution (V/F), 1.26 1/h for the absorption constant (KA) and 25.7 h for the mean plasma terminal half‐life. Simulations showed that the median trough steady‐state concentrations of 228 ng/mL were reached after five, one or 6 days following a single initial dose of 0.05, 0.1 and 0.2 mg/kg each followed by 0.05 mg/kg/day.  相似文献   

16.
Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum‐coated colon‐targeted tablets of RDZ and to determine the pharmacokinetics of this delayed‐release formulation in cats. Guar gum‐coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean Cmax 28.9 μg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum‐coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady‐state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.  相似文献   

17.
Meloxicam is a nonsteroidal anti‐inflammatory drug commonly used in avian species. In this study, the pharmacokinetic parameters for meloxicam were determined following single intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations of the drug (1 mg/kg·b.w.) in adult African grey parrots (Psittacus erithacus; n = 6). Serial plasma samples were collected and meloxicam concentrations were determined using a validated high‐performance liquid chromatography assay. A noncompartmental pharmacokinetic analysis was performed. No undesirable side effects were observed during the study. After i.v. administration, the volume of distribution, clearance and elimination half‐life were 90.6 ± 4.1 mL/kg, 2.18 ± 0.25 mL/h/kg and 31.4 ± 4.6 h, respectively. The peak mean ± SD plasma concentration was 8.32 ± 0.95 μg/mL at 30 min after i.m. administration. Oral administration resulted in a slower absorption (tmax = 13.2 ± 3.5 h; Cmax = 4.69 ± 0.75 μg/mL) and a lower bioavailability (38.1 ± 3.6%) than for i.m. (78.4 ± 5.5%) route. At 24 h, concentrations were 5.90 ± 0.28 μg/mL for i.v., 4.59 ± 0.36 μg/mL for i.m. and 3.21 ± 0.34 μg/mL for p.o. administrations and were higher than those published for Hispaniolan Amazon parrots at 12 h with predicted analgesic effects.  相似文献   

18.
The aim of this study was to sequence all exons of the ABCB1 (MDR1) gene in cats that had experienced adverse reactions to P‐glycoprotein substrate drugs (phenotyped cats). Eight phenotyped cats were included in the study consisting of eight cats that experienced central nervous system toxicosis after receiving ivermectin (n = 2), a combination product containing moxidectin and imidacloprid (n = 3), a combination product containing praziquantel and emodepside (n = 1) or selamectin (n = 2), and 1 cat that received the product containing praziquantel and emodepside but did not experience toxicity (n = 1). Fifteen exons contained polymorphisms and twelve exons showed no variation from the reference sequence. The most significant finding was a nonsense mutation (ABCB11930_1931del TC) in one of the ivermectin‐treated cats. This cat was homozygous for the deletion mutation. All of the other phenotyped cats were homozygous for the wild‐type allele. However, 14 missense mutations were identified in one or more phenotyped cats. ABCB11930_1931del TC was also identified in four nonphenotyped cats (one homozygous and three heterozygous for the mutant allele). Cats affected by ABCB11930_1931del TC would be expected to have a similar phenotype as dogs with the previously characterized ABCB1‐1Δ mutation.  相似文献   

19.
The purpose of this study was to compare the pharmacokinetics of meloxicam in mature swine after intravenous (i.v.) and oral (p.o.) administration. Six mature sows (mean bodyweight ± standard deviation = 217.3 ± 65.68 kg) were administered an i.v. or p.o. dose of meloxicam at a target dose of 0.5 mg/kg in a cross‐over design. Plasma samples collected up to 48 h postadministration were analyzed by high‐pressure liquid chromatography and mass spectrometry (HPLC‐MS) followed by noncompartmental pharmacokinetic analysis. Mean peak plasma concentration (CMAX) after p.o. administration was 1070 ng/mL (645–1749 ng/mL). TMAX was recorded at 2.40 h (0.50–12.00 h) after p.o. administration. Half‐life (T½ λz) for i.v. and p.o. administration was 6.15 h (4.39–7.79 h) and 6.83 h (5.18–9.63 h), respectively. The bioavailability (F) for p.o. administration was 87% (39–351%). The results of this study suggest that meloxicam is well absorbed after oral administration.  相似文献   

20.
The purpose of this study was two-fold: I) to determine the pharmacokinetic profile of meloxicam (MLX) in geese after intravenous (IV) and oral (PO) administration and II) to assess tissue residues in muscle, heart, liver, lung, and kidney. Ten clinically normal female Bilgorajska geese were divided into two groups (treated, n = 8; control, n = 2). Group 1 underwent a 3-phase parallel study with a 1-week washout period. In phase I, animals received MLX (0.5 mg/kg) by IV administration; the blood was collected up to 48 hr. In phases II and III geese were treated orally at the same dosage for the collection of blood and tissue samples, respectively. Group 2 served as control. After the extraction procedure, a validated HPLC method with UV detection was used for plasma and organ analysis. The plasma concentrations were quantifiable up to 24 hr after both the administrations. The elimination phase of MLX from plasma was similar in both the administration groups. The clearance was slow (0.00975 L/hr*Kg), the volume of distribution small (0.0487 L/kg), and the IV half-life was 5.06 ± 2.32 hr. The average absolute PO bioavailability was 64.2 ± 24.0%. Residues of MLX were lower than the LOQ (0.1 µg/kg) in any tested tissue and at any collection time. The dosage used in this study achieved the plasma concentration, which provides analgesia in Hispaniolan Amazon parrots for 5 out of 24 hr after PO administration. MLX tissue concentrations were below the LOD of the assay in tissue (0.03 µg/ml). A more sensitive technique might be necessary to determine likely residue concentrations in tissue.  相似文献   

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