Pharmacokinetics of oral gabapentin alone or co-administered with meloxicam in ruminant beef calves

Coetzee, Johann F.; Mosher, Ruby A.; Kohake, L. E.; Cull, Charley A.; Kelly, L.; Mueting, Stacy L.; KuKanich, Butch

doi:10.1016/j.tvjl.2010.08.008

Cited by 64 publications

(52 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The onset and duration of the anti-allodynic effect of GBP following a single intraperitoneal injection were dose-related and in line with its known pharmacokinetic and pharmacodynamic characteristics [44,76–78] . The anti-allodynic effect of GBP is not likely to be attributable to the side-effect (sedation) induced by high doses in our study, because no effect on motor coordination was observed after administration of 100 mg/ kg, indicating that GBP is more tolerable than ketamine that has severe motor side-effects [32] .…”

Section: Discussionmentioning

confidence: 77%

Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

Yang

Han

et al. 2014

Neurosci. Bull.

View full text Add to dashboard Cite

Intractable central post-stroke pain (CPSP) is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV (ITC) injection. Then, we evaluated the efficacy of gabapentin (GBP), an anticonvulsant that binds the voltage-gated Ca2+ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration (1, 10, or 100 mg/kg) on day 7 post-ITC, with significant effects lasting at least 5 h for the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness (drug tolerance) at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.

show abstract

Section: Discussionmentioning

confidence: 77%

Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

Yang

Han

et al. 2014

Neurosci. Bull.

View full text Add to dashboard Cite

show abstract

“…Evaluation of meloxicam revealed that a mean CMAX of 1.9 μg/mL (range 1.3–2.1 μg/mL) occurred approximately 24 h (range 12–24 h) following oral administration. The mean TMAX in the present study is longer than those previously reported, and lower mean AUC values were observed (Coetzee et al ., , ; Mosher et al ., ). In the previously mentioned studies, the method of oral administration was a suspension of crushed tablets in water, whereas in our study, meloxicam tablets were administered whole and placed in a bolus filled with whey powder.…”

Section: Discussionmentioning

confidence: 97%

“…Neuropathic pain is thought to be resistant to the effects of NSAIDs; thus, there is a need for investigation of drugs, such as gabapentin, that are designated for the treatment of nerve damage. Gabapentin is commonly prescribed for the treatment of chronic pain in humans; moreover, it has been previously documented that gabapentin has an elimination half‐life of 11 h in cattle with the potential to mitigate chronic pain syndromes, such as lameness, in cattle (Coetzee et al ., ). It is also possible that dehorning causes both inflammatory and neuropathic pain, suggesting that concurrent dosing of a NSAID and a neuropathic pain reliever may provide superior analgesia.…”

Section: Introductionmentioning

confidence: 97%

“…It is also possible that dehorning causes both inflammatory and neuropathic pain, suggesting that concurrent dosing of a NSAID and a neuropathic pain reliever may provide superior analgesia. An investigation in the target species, bovine, found that gabapentin powder dosed with meloxicam PO resulted in plasma concentrations above the minimum concentration believed to provide analgesic effects (Coetzee et al ., ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The pharmacokinetics and effects of meloxicam, gabapentin, and flunixin in postweaning dairy calves following dehorning with local anesthesia

Glynn

Coetzee

Edwards‐Callaway

et al. 2013

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

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.

show abstract

“…Plasma concentrations of meloxicam ( m/z 352.09→114.90) were determined with high-pressure liquid chromatography (Shimadzu Prominence, Shimadzu Scientific Instruments) and mass spectrometry (API 2000, Applied Biosystems) as previously described [13,46]. With a limit of quantification of 0.025 μg/mL, the standard curve was linear from 0.025 μg/mL to 10 μg/mL and was accepted if the correlation coefficient exceeded 0.99 and predicted values were within 15% of the actual values.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and effect of intravenous meloxicam in weaned Holstein calves following scoop dehorning without local anesthesia

et al. 2012

Self Cite

View full text Add to dashboard Cite

BackgroundDehorning is a common practice involving calves on dairy operations in the United States. However, less than 20% of producers report using analgesics or anesthetics during dehorning. Administration of a systemic analgesic drug at the time of dehorning may be attractive to dairy producers since cornual nerve blocks require 10 – 15 min to take effect and only provide pain relief for a few hours. The primary objectives of this trial were to (1) describe the compartmental pharmacokinetics of meloxicam in calves after IV administration at 0.5 mg/kg and (2) to determine the effect of meloxicam (n = 6) or placebo (n = 6) treatment on serum cortisol response, plasma substance P (SP) concentrations, heart rate (HR), activity and weight gain in calves after scoop dehorning and thermocautery without local anesthesia.ResultsPlasma meloxicam concentrations were detectable for 50 h post-administration and fit a 2-compartment model with a rapid distribution phase (mean T½α = 0.22 ± 0.087 h) and a slower elimination phase (mean T½β = 21.86 ± 3.03 h). Dehorning caused a significant increase in serum cortisol concentrations and HR (P < 0.05). HR was significantly lower in the meloxicam-treated calves compared with placebo-treated calves at 8 h (P = 0.039) and 10 h (P = 0.044) after dehorning. Mean plasma SP concentrations were lower in meloxicam treated calves (71.36 ± 20.84 pg/mL) compared with control calves (114.70 ± 20.84 pg/mL) (P = 0.038). Furthermore, the change in plasma SP from baseline was inversely proportional to corresponding plasma meloxicam concentrations (P = 0.008). The effect of dehorning on lying behavior was less significant in meloxicam-treated calves (p = 0.40) compared to the placebo-treated calves (P < 0.01). Calves receiving meloxicam prior to dehorning gained on average 1.05 ± 0.13 kg bodyweight/day over 10 days post-dehorning compared with 0.40 ± 0.25 kg bodyweight/day in the placebo-treated calves (p = 0.042).ConclusionsTo our knowledge, this is the first published report examining the effects of meloxicam without local anesthesia on SP, activity and performance of calves post-dehorning. These findings suggest that administration of meloxicam alone immediately prior to dehorning does not mitigate signs of acute distress but may have long term physiological, behavior and performance effects.

show abstract

Pharmacokinetics of oral gabapentin alone or co-administered with meloxicam in ruminant beef calves

Cited by 64 publications

References 17 publications

Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

The pharmacokinetics and effects of meloxicam, gabapentin, and flunixin in postweaning dairy calves following dehorning with local anesthesia

Pharmacokinetics and effect of intravenous meloxicam in weaned Holstein calves following scoop dehorning without local anesthesia

Contact Info

Product

Resources

About