Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in horses with induced arthritis in the right carpal joint

Toutain, Pierre‐Louis; Cester, C. C.

doi:10.2460/ajvr.2004.65.1533

Cited by 100 publications

(98 citation statements)

References 16 publications

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“…This result indicated the advantage of topical administration and also illustrated that the meloxicam concentration in SF following transdermal administration might serve as a better indicator than plasma concentration of the drug's therapeutic efficiency. The reported dose effects for meloxicam in horses corresponded to a plasma concentration between 130 ng/mL and 195 ng/mL [12] . Our results of SF concentrations higher than 100 ng/mL by transdermal administration should be adequate to meet therapeutic needs.…”

Section: Discussionmentioning

confidence: 99%

“…A blood sample of 0.5 mL was obtained at 0 (predose), 2, 4, 8, 12, 24, 36, 48, 72, and 96 h after topical dosing. An SF sample of 50 µL was collected in the same way as described in the "Oral administration" section at 0 (predose), 8,12,24,48,72, and 96 h, respectively. All of the samples were stored at −20ºC until analysis.…”

Section: Topical Administrationmentioning

confidence: 99%

“…The needle was advanced until no resistance could be felt, which indicated successful entry into the joint space. An SF sample of 50 µL was collected from the stifle joints of the left and right hind legs, respectively, at 0 (predose), 4,8,12,24,48,72, and 96 h post dose. The SF samples were stored at -20 ºC until analysis.…”

Section: Oral Administrationmentioning

confidence: 99%

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Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Yuan

Chen

et al. 2009

Acta Pharmacol Sin

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Aim:The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs. Methods: The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic parameters were calculated using the Topfit 2.0 program. Results: The pharmacokinetic results showed that AUC 0-t (23.9±8.26 µg·h·mL -1 ) in plasma after oral administration was significantly higher than after transdermal delivery (1.00±0.43 µg·h·mL -1 ). In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration. Conclusion: The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.

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Section: Discussionmentioning

confidence: 99%

Section: Topical Administrationmentioning

confidence: 99%

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Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Yuan

Chen

et al. 2009

Acta Pharmacol Sin

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“…The tendency of this type of NSAID to accumulate in inflammatory exudates may explain a longer duration of action than that anticipated based on elimination half -life (Lees et al 1987). Subsequent investigation of the pharmacodynamics and pharmacokinetics of meloxicam in the horse indicates that once daily dosing at 0.6 mg/kg bodyweight may be an appropriate dosing regimen (Lees et al 1991, Toutain andCester 2004). The suggested once daily dose regimen was investigated in this randomised, blinded, positive controlled clinical study, where the tentative diagnosis included a range of clinical conditions either of acute or chronic duration characterised by varying degrees of severity.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the clinical efficacy, safety and palatability of meloxicam (Metacam) treatment in horses with musculosceletal disorders

Friton¹,

Philipp²,

Kleemann³

2006

PHK

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SummaryThis GCP(v) multi centre blinded positive controlled study investigated under field conditions the clinical efficacy, safety and palatability of meloxicam in horses suffering from musculoskeletal disorders. The efficacy of meloxicam (Metacam ® ) at the recommended dose of 0.6 mg/kg body weight administered once daily was investigated (n=100) in comparison to vedaprofen (Quadrisol ® , n=97). Lameness at a trot, walk and rest was recorded before initiation of therapy on Day 1, after a 5, 10 or 14 day treatment period and during the follow-up examination, performed 2 to 4 days after the respective last treatment. The duration of treatment (5, 10 or 14 days) was decided by the veterinarian depending on the clinical condition. Furthermore palatability and relapse rates were recorded. Significantly better results (p≤0.01) for "lameness at a trot" (primary clinical variable) after 14 days of treatment, and at the follow-up examination (p≤0.001), were found in the meloxicam group compared to the reference group. Significant differences (p≤0.05) in "lameness at walk" occurred in favour of meloxicam at the follow-up examination on Day 14. A significant superiority in lameness at a trot (p≤0.001) and walk (p≤0.01) was revealed in favour of meloxicam for the evaluation at the time point when therapy was judged no longer necessary. Fewer meloxicam cases showed relapse to lameness (p≤0.05). Furthermore, meloxicam was superior (p≤0.001) with regard to overall efficacy and palatability. No adverse events occurred in the meloxicam group compared to two cases in the reference group. The results indicate that 0.6 mg meloxicam/kg bodyweight administered orally once daily is an efficacious, safe, easy to use, and highly palatable NSAID treatment for reduction of inflammation and relief of pain associated with lameness in both acute and chronic musculoskeletal disorders and soft tissue lesions. Keywords

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“…The pharmacokinetic-pharmacodynamic relationship and dose response to MEL in horses with induced carpal arthritis has been previously reported (Toutain and Cester, 2004). Based on this work, the reported half maximal effective concentration (EC50) for MEL in the plasma of lame horses is approximately 0.2 μg/mL.…”

Section: Meloxicam and Gabapentin Plasma Concentrationsmentioning

confidence: 93%

Impact of oral meloxicam administered alone or in combination with gabapentin on experimentally induced lameness in beef calves1

Coetzee

Mosher

Anderson

et al. 2014

Journal of Animal Science

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This study examined the pharmacokinetics and analgesic effect of oral meloxicam (MEL) administered alone or in combination with gabapentin (GABA) in an experimental bovine lameness model. Eighteen male British × Continental beef calves aged 4 to 6 mo and weighing 297 to 392 kg were randomly assigned to receive either 1) 0.5 mg/kg lactose monohydrate placebo (PLBO; n = 6), 2) 0.5 mg/kg MEL (n = 6), or 3) 0.5 mg/kg MEL combined with 15 mg/kg GABA (MEL-GABA; n = 6) once daily for 4 d. The first treatment was administered 4 h after a chemical synovitis/arthritis was induced with injection of 15 mg amphotericin B into the left hind lateral distal interphalangeal joint. Changes in activity were evaluated continuously with pedometers. Contact force, contact area, contact pressure, impulse, and stride length were recorded once daily with a pressure mat and visual lameness scores were determined by a masked observer using a 5-point scale.Cortisol and drug concentrations were determined daily by immunoassay and HPLC-mass spectrometry, respectively. Outcomes were compared statistically using a random effects mixed model and analysis of covariance. There was a positive association between lameness scores and serum cortisol concentrations (P = 0.02) and a negative association between lameness score and step count (P < 0.0001), total force (P = 0.001), force applied to the lateral claw (P= 0.02), contact pressure (P = 0.005), and impulse of the lateral claw (P = 0.01).Step count was greater in MEL calves compared with PLBO (P = 0.008) and MEL-GABA (P = 0.04) calves. Impulse was greater in the MEL-GABA calves compared with the PLBO calves (P = 0.03). There was an inverse relationship between plasma MEL concentrations and lameness score (P = 0.02) and a positive association between MEL concentrations and force applied to the lateral claw (P = 0.03), total contact pressure (P = 0.03), and impulse on the lateral claw (P = 0.02). There was a tendency towards a positive association between GABA concentrations, total impulse, and impulse on the lateral claw (P = 0.08) and a negative associate between GABA concentrations and step count (P = 0.08). The results of this study suggest that MEL administered alone or in combination with GABA reduced the severity of lameness in calves following induction of lameness with amphotericin B. These findings have implications for developing analgesic protocols in lame calves that address both production and welfare concerns.

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Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in horses with induced arthritis in the right carpal joint

Abstract: Results of this study suggest that meloxicam is a potent anti-inflammatory drug in horses. A dosage of 0.6 mg/kg/d would be appropriate for use in a clinical study.

Cited by 100 publications

References 16 publications

Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Investigation of the clinical efficacy, safety and palatability of meloxicam (Metacam) treatment in horses with musculosceletal disorders

Impact of oral meloxicam administered alone or in combination with gabapentin on experimentally induced lameness in beef calves1

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