Pharmacokinetics of meloxicam in adult goats: a comparative study of subcutaneous,oral and intravenous administration

AIMS: To determine the plasma disposition of meloxicam in goats following S/C, oral or I/V administration at a single dose of 0.5?mg/kg bodyweight.

METHODS: Five healthy Saanen goats, aged 12–14 months and weighing 35–40?kg, were used for a three phase cross-over design with a 10-day washout period, with meloxicam administered I/V, then orally and S/C. Heparinised blood samples (5?mL) were collected from all animals prior to drug administration (0 hours) and subsequently up to 96 hours. Concentrations of meloxicam in plasma were measured using high performance liquid chromatography. Concentration-time curves were fitted and pharmacokinetic parameters were estimated for each administration group.

RESULTS: Subcutaneous administration of meloxicam exhibited unique plasma distribution characteristics that differed from oral and I/V administration. Mean peak plasma concentrations were greater (1.91 (SD 0.39) vs. 0.71 (SD 0.17) µg/mL) and the time to reach them shorter (3.20 (SD 1.64) vs. 14.33 (SD 2.19) hours) following S/C compared with oral administration (p<0.05). The terminal half-life was longer (15.16 (SD 4.74) vs. 10.69 (SD 1.49) hours) and the MRT was shorter (15.67 (SD 2.37) vs. 24.33 (SD 3.12) hours) following S/C than oral administration (p<0.05), but bioavailability was similar (98.24 (SD 9.62) vs. 96.49 (SD 10.71)%).

CONCLUSION AND CLINICAL RELEVANCE: Subcutaneous administration of meloxicam resulted in long-term presence of drug at high concentration in goat plasma. This unique plasma disposition characteristic may offer an advantage in some clinical cases towards potentially improving the treatment efficacy in goats.     

Effect of meloxicam administration after calving on milk production,acute phase proteins,and behavior in dairy cows

Calving is an intrinsically risky process that can cause welfare and economic problems. The objective of this study was to assess the effect of the nonsteroidal anti-inflammatory drug meloxicam on various physiological and behavioral measures which can be related to pain in cattle. Sixty Friesian dairy cows from first to sixth parity were studied around calving and were randomly allocated into 2 homogeneous groups relative to parity and treated with either meloxicam or a placebo after calving. Treatments were administered on average 3.4 hours after calving, within a maximum of 6 hours. Calf positions at calving and calving assistance (unassisted or easy manual pull) were recorded. Milk production, rectal temperature, and activity (calculated as the number of steps per hour) were measured on each cow. From a subsample of 20 cows, haptoglobin (Hp) and serum amyloid A (SAA) concentrations were also obtained. The following behaviors were observed on video recordings: posture, changing posture, location of cow in pen, feeding, and tail up behaviors 2 days before and after calving. Statistical analysis was carried out with the SAS software using MIXED or GENMOD procedures. Most variables showed a parity and/or time effect around calving. This study did not demonstrate any significant effect of meloxicam on milk production or on acute phase responses of Hp and SAA. However, postcalving activity was significantly increased in meloxicam-treated heifers.     

Dose range finding study for the efficacy of meloxicam administered prior to sodium urate-induced synovitis in cats

ObjectiveTo determine the lowest efficacious dose of oral meloxicam for relieving pain in cats with a sodium urate (SU)-induced acute inflammatory synovitis.Study designRandomized, blinded, controlled, and four-way crossover study.AnimalsEight surgically neutered cats (four males, four females) paired according to sex.MethodsEach pair of cats was treated with 0 (placebo), 0.025, 0.05, or 0.075 mg kg^?1 oral meloxicam once daily for 4 days prior to injection, into alternating stifles, of 1 mL of 20 mg mL^?1 SU crystals, beginning with the right stifle. Each cat received each of the four treatments, separated by at least 21 days. Analgesic efficacy was evaluated based on objective (e.g., pressure mat data total force, contact pressure, and contact area) and subjective (e.g., scores for Analgesia Scale [AS], Lameness Scale [LS], and Visual Analog Scale [VAS]) outcome measures for pain assessment. All outcome measures were recorded before and during 30 hours after SU injection. The pre-defined primary outcome measure was the area under the response–time curve (AUC_0–30 hours) of the total force of the injected limb. Data were analyzed by analysis of variance. A sequential test procedure was applied and the test sequence stopped in case of a nonsignificant result.ResultsMeloxicam at doses of 0.05 and 0.075 mg kg^?1 day^?1 PO was significantly different from placebo for the pre-defined primary outcome measure (i.e., AUC_0–30 hours of total force). All tested meloxicam doses were lower than placebo for the subjective outcome measures (i.e., AUC_0–30 hours of AS, LS, and VAS).Conclusions and clinical relevanceThe lowest efficacious dose of meloxicam for relieving pain in cats with an SU-induced synovitis was 0.05 mg kg^?1 day^?1 PO according to the pre-defined primary outcome measure. However, lower doses may also be effective as seen in the subjective outcome measures.     

Preliminary observations on the effects of Meloxicam in a new model for acute intra-articular inflammation in dogs

The effects of intra-articular injection, on two occasions, 3 weeks apart, of the contrast agent Urografin on the cytological and biochemical characteristics of synovial fluid (SF) were examined in two studies in dogs. The first study provided baseline data in two non-medicated dogs. The second study used a cross-over design whereby 4 dogs received a 7-day oral treatment with either a placebo or meloxicam (0.2 mg/kg body weight daily) with a washout period of 3 weeks, in order to determine the effect of this new non-steroidal anti-inflammatory drug (NSAID) on the response to Urografin injection. SF samples were collected under general anaesthesia prior to and at 24 and 72 h after each Urografin injection. The volume, relative viscosity, white blood cell count and concentrations of protein, lactate dehydrogenase (LDH) and hyaluronic acid of these samples were determined.The results from both studies indicate that intra-articular injection of Urografin provoked a mild local transient inflammatory response, the most dramatic evidence of which was an increase in the white blood cell count in the SF after 24 h. In the second study, comparison of the synovial fluid measurements of the placebo-treated dogs at 24 h after Urografin injection with those prior to injection revealed significant increases in SF volume, white blood cell count, protein concentration and LDH activity and a significant reduction in relative viscosity. At 72 h after injection, only the white blood cell count and relative viscosity were significantly different from the pre-injection values. All of these measurements were, however, associated with high coefficients of variation, which must be taken into account in assessing the usefulness of the model for drug-testing purposes. Nevertheless, the administration of meloxicam significantly reduced the SF volume and white blood cell count at 24 h relative to the effects of concurrent placebo treatment. The general health status of the animals was not disturbed at any time as assessed by clinical and haematological observations. No adverse reactions were observed.Abbreviations LDH lactate dehydrogenase - NSAID non-steroidal anti-inflammatory drug - SF synovial fluid - WBC white blood cell count     

Development of a lameness model in sheep for assessing efficacy of analgesics

Objective To develop a lameness model to assess the efficacy of analgesics for alleviating pain, swelling and systemic signs of inflammation in sheep. Procedures The response to subcutaneous injection of 0.1 or 0.2 mL turpentine in a forelimb pastern (n = 4 ewes per dose) was examined at 0, 3, 6, 24, 48 and 72 h. In a second experiment, responses were measured at 0, 2, 4, 6, 8, 10, 12 and 24 h in ewes receiving 0.1 mL turpentine ± meloxicam 1 mg/kg IV at 0 h (n = 6 per group). Responses measured included forceplate pressure, skin temperature, limb circumference, nociception, leucocyte count, neutrophil : lymphocyte ratio, haptoglobin and daily feed intake. Results Turpentine injection caused a decrease in weight borne on the treated limb, increased skin temperature, increased sensitivity at the injection site and leucocytosis by 2 h and increased limb circumference by 4 h. Weight borne and sensitivity of the injected limb returned to control levels after around 24 h, whereas tissue swelling, elevated skin temperature and elevated haptoglobin levels persisted for at least 72 h. Treatment with meloxicam improved weight borne by and tolerance to pressure exerted on the turpentine‐injected limb. Conclusions The local and systemic signs of inflammation and pain, temporary reduction in function of the affected limb and partial amelioration of some of these changes by the dose of meloxicam used here suggest that injection of turpentine in the lower forelimb provides a suitable model for examining the efficacy of analgesics for alleviation of pain and inflammation in sheep.     

The effect of different combinations of local anaesthesia,sedative and non-steroidal anti-inflammatory drugs on daily growth rates of dairy calves after disbudding

AIM: To assess the effect of sedation and local anaesthesia (LA) at disbudding, and the addition of meloxicam or ketoprofen treatment, on weight gain in dairy calves following disbudding.

METHODS: Friesian-Jersey cross calves, from four dairy farms, were enrolled when 3–6 weeks old. All calves (n=271) were disbudded by veterinary personnel and randomly assigned to six groups: 136 were disbudded without sedation or LA, of which 31 received 20 mg meloxicam S/C and 75 received 150 mg ketoprofen I/M. A further 135 were disbudded with sedation (0.25 mg/kg xylazine I/M) and LA, of which 30 also received meloxicam and 75 received ketoprofen. Calves were weighed 3 days before, and 15 and 30 days after, disbudding (Day 0). Daily weight gain was analysed using mixed models and ANOVA.

RESULTS: Complete results were obtained from 263 calves. From Day ?3 to Day 15, the growth rate of calves disbudded without pain relief (0.53 (95% CI=0.47–0.60) kg/day) was less that of calves disbudded with some form of pain relief (0.65 (95% CI=0.62–0.68) kg/d; p=0.004). There was no difference between the effect of meloxicam or ketoprofen (p=1.00). An interaction between use of sedation and LA and additional non-steroidal anti-inflammatory drugs (NSAID) meant that NSAID treatment did not increase growth rates in calves disbudded with sedation and LA but did increase growth rates for calves disbudded without pain relief (p<0.05). From Day 16 to Day 30 there was no effect of NSAID treatment on growth rate, but calves receiving LA and sedation grew faster (0.74 (95% CI=0.69–0.80) kg/day) than calves disbudded without LA and sedation (0.66 (95% CI=0.61–0.71) kg/day; p=0.018). From Day ?3 to Day 30, calves disbudded with sedation and LA grew faster (0.71 (95%CI=0.64–0.77) kg/day) than calves disbudded without sedation and LA (0.60 (95% CI=0.55–0.65) kg/day; p=0.011). However, addition of NSAID to sedation and LA made no further difference to growth rates (p=0.69).

CONCLUSIONS: Dairy calves disbudded with no pain relief had slower growth rates than calves receiving pain relief. From Day 15 to 30 calves given no pain relief, or NSAID alone, grew more slowly than those receiving sedation and LA at disbudding. The addition of NSAID treatment to sedation and LA did not further increase growth rates.

CLINICAL RELEVANCE: This study adds to the evidence that pain management when disbudding is beneficial for calf productivity as well as calf welfare.     

Effect of non-steroidal anti-inflammatory drugs on glomerular filtration rate and urinary N-acetyl-β-D-glucosaminidase activity in cats after dental surgery

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 (f_R), 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, f_R 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.