Pharmacokinetic/pharmacodynamic modeling of ketoprofen and flunixin at piglet castration and <scp>tail‐docking</scp>

Nixon, Emma; Chittenden, Jason; Baynes, Ronald E.; Messenger, Kristen M.

doi:10.1111/jvp.13083

Cited by 5 publications

(2 citation statements)

References 43 publications

(70 reference statements)

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“…The toxicity of meloxicam in humans and different mammalian species has been well-studied in laboratory animals, companion animals, cattle, and pigs [ 79 , 80 , 81 , 82 ], and meloxicam has consistently been shown to be safe for piglets and adult pigs [ 79 , 80 , 81 ]. It has also been shown to be less toxic than other NSAIDs, as it is a specific COX-2 antagonist [ 82 , 83 , 84 , 85 ]. This study confirmed the safety of topical 4% lidocaine and 0.3% meloxicam, as there were no safety issues, even in piglets receiving three times the nominal dose daily for three subsequent daily treatments.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Lidocam Topical Gel (4% Lidocaine—0.3% Meloxicam) for Pain and Inflammation Management during Castration and Tail Docking in Piglets

Nagel,

Ralston,

Hanson

et al. 2024

Animals

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(1) Background: It has been well established that castration and tail docking are both painful during and following the procedure, yet there are limited convenient and effective products to address both short-term and long-term pain. Lidocam Topical Gel (LTG) (4% lidocaine and 0.3% meloxicam) was developed to address industry needs for an effective and safe product to address animal welfare concerns regarding castration and tail docking in piglets. (2) Methods: Study 1: Male piglets aged 4–8 days of age were treated with LTG (n = 30) or a control gel (n = 30). Approximately 30 min after application of the gel, the piglets were surgically castrated and tail docked. The efficacy of pain control during the surgical procedures and post-procedure (24 h) pain and inflammation control were evaluated using both behavioral and physiological measurements. Study 2: Meloxicam residue depletion following LTG treatment was followed for 28 days. Study 3: Clinical and pathological safety were evaluated in five groups of eight piglets receiving LTG with: (1) no treatment, (2) nominal topical dose, (3) two times the nominal topical dose, (4) three times the nominal topical dose, and 5) one times the nominal topical dose and 2 mL of LTG by oral gavage daily for 3 days. (3) Results: LTG-treated piglets had a significant reduction in electrocutaneous stimulation response before the procedures and 4 and 24 h post-procedures. Stress vocalization intensity and duration were less in piglets receiving LTG during the surgical procedures. Plasma cortisol and substance P were significantly lower in LTG-treated piglets 3 h after castration and tail docking. The weight and average daily gain were significantly increased in piglets receiving LTG. LTG did not interfere with wound healing or cause irritation at the application sites. There were no abnormal clinical or pathological findings associated with the use of LTG at three times the nominal dose given daily for three days. As meloxicam persisted in the application site tissue, a slaughter withdrawal time of 24 days was determined. (4) Conclusions: When applied to the skin 30 min before castration and tail docking, LTG is effective in surgical pain control and provides post-surgical pain control for up to 24 h. LTG is safe for use in piglets and provides an acceptable withdrawal time for commercial use. LTG is a potentially effective product for commercial use for piglet castration and tail docking.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Lidocam Topical Gel (4% Lidocaine—0.3% Meloxicam) for Pain and Inflammation Management during Castration and Tail Docking in Piglets

Nagel,

Ralston,

Hanson

et al. 2024

Animals

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“…To date, only a few studies have investigated the efficacy of these drugs in pigs housed under different conditions and treatment regimens [ 18 ]. Most of these studies have focused on their efficacy in relieving pain in piglet castration and their anti-inflammatory potential in experimental models of inflammation [ 18 , 19 , 20 ]. The use of NSAIDs and their effects on the development of gastric lesions in fattening pigs have been little studied.…”

Section: Introductionmentioning

confidence: 99%

A Preliminary Study on the Relationship between Gastric Lesions and Anti-Inflammatory Drug Usage in Heavy Pigs

Ghidini,

Scali,

Romeo

et al. 2023

Veterinary Sciences

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Gastric lesions in pigs cause welfare and economic losses. Their prevalence in heavy pigs reared for premium products (e.g., Parma ham) requires further investigation. Stress, nutrition, and farm management are known risk factors, but the effects of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) are largely unknown. The aim of this study was to evaluate the prevalence of gastric lesions in Italian heavy pigs and their possible association with the use of anti-inflammatory drugs. A total of 9371 pig stomachs from 76 farms were evaluated. Among these, 20.3% showed no lesions, while 30.7%, 42.1%, and 6.8% were scored 1, 2 and 3, respectively. A tendency for an inverse relationship with farm size emerged. The use of steroids and NSAIDs was estimated by calculating a treatment incidence per 1000 (TI1000) in a subset of 36 farms. At least one prescription for NSAIDs and/or steroids was found in 80.6% of the farms (55.6% used NSAIDs and 63.9% used steroids). Median TI1000 was 0.07 (range: 0–30.1) and 0.18 (range: 0–6.2) for NSAIDs and steroids, respectively. Gastric scores were positively associated with NSAID use, but not with steroid use. Although the role of these drugs in gastric lesions needs to be further clarified, these findings suggest a cautious use of non-selective NSAIDs.

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Pharmacokinetic/pharmacodynamic modeling of ketoprofen and flunixin at piglet castration and tail‐docking

Nixon

Chittenden

Baynes

et al. 2022

Vet Pharm & Therapeutics

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This study performed population‐pharmacokinetic/pharmacodynamic (pop‐PK/PD) modeling of ketoprofen and flunixin in piglets undergoing routine castration and tail‐docking, utilizing previously published data. Six‐day‐old male piglets (8/group) received either ketoprofen (3.0 mg/kg) or flunixin (2.2 mg/kg) intramuscularly. Two hours post‐dose, piglets were castrated and tail docked. Inhibitory indirect response models were developed utilizing plasma cortisol or interstitial fluid prostaglandin E2 (PGE2) concentration data. Plasma IC50 for ketoprofen utilizing PGE2 as a biomarker was 1.2 μg/ml, and ED50 for was 5.83 mg/kg. The ED50 calculated using cortisol was 4.36 mg/kg; however, the IC50 was high, at 2.56 μg/ml. A large degree of inter‐individual variability (124.08%) was also associated with the cortisol IC50 following ketoprofen administration. IC50 for flunixin utilizing cortisol as a biomarker was 0.06 μg/ml, and ED50 was 0.51 mg/kg. The results show that the currently marketed doses of ketoprofen (3.0 mg/kg) and flunixin (2.2 mg/kg) correspond to drug responses of 33.97% (ketoprofen‐PGE2), 40.75% (ketoprofen‐cortisol), and 81.05% (flunixin‐cortisol) of the maximal possible responses. Given this information, flunixin may be the best NSAID to use in mitigating castration and tail‐docking pain at the current label dose.

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Pharmacokinetic/pharmacodynamic modeling of ketoprofen and flunixin at piglet castration and tail‐docking

Cited by 5 publications

References 43 publications

Efficacy and Safety of Lidocam Topical Gel (4% Lidocaine—0.3% Meloxicam) for Pain and Inflammation Management during Castration and Tail Docking in Piglets

Efficacy and Safety of Lidocam Topical Gel (4% Lidocaine—0.3% Meloxicam) for Pain and Inflammation Management during Castration and Tail Docking in Piglets

A Preliminary Study on the Relationship between Gastric Lesions and Anti-Inflammatory Drug Usage in Heavy Pigs

Pharmacokinetic/pharmacodynamic modeling of ketoprofen and flunixin at piglet castration and tail‐docking

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