Stereospecific pharmacodynamics and pharmacokinetics of carprofen in the dog

McKellar, Quintin; Delatour, P.; Lees, P.

doi:10.1111/j.1365-2885.1994.tb00276.x

Cited by 82 publications

(112 citation statements)

References 16 publications

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“…36 It has high plasma concentration in cats, achieving levels from 25 to 50 mg/L after administration of a low dose of 4 mg/kg during the first 7 h. 37 However, in dogs, the plasma levels were inferior (between 2 and 15 mg/L) for the same dose. 38 In humans, the plasma levels after a single oral dose of 150 mg rose to 10 mg/L during the first 5 h after administration. 39 The half lethal dose (LD 50 ) of carprofen in mice is 282 mg/kg and in rats it is 149 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay

et al. 2013

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ObjectivesLead antituberculosis (anti-TB) molecules with novel mechanisms of action are urgently required to fuel the anti-TB drug discovery pipeline. The aim of this study was to validate the use of the high-throughput spot culture growth inhibition (HT-SPOTi) assay for screening libraries of compounds against Mycobacterium tuberculosis and to study the inhibitory effect of ibuprofen (IBP) and the other 2-arylpropanoic acids on the growth inhibition of M tuberculosis and other mycobacterial species.MethodsThe HT-SPOTi method was validated not only with known drugs but also with a library of 47 confirmed anti-TB active compounds published in the ChEMBL database. Three over-the-counter non-steroidal anti-inflammatory drugs were also included in the screening. The 2-arylpropanoic acids, including IBP, were comprehensively evaluated against phenotypically and physiologically different strains of mycobacteria, and their cytotoxicity was determined against murine RAW264.7 macrophages. Furthermore, a comparative bioinformatic analysis was employed to propose a potential mycobacterial target.ResultsIBP showed antitubercular properties while carprofen was the most potent among the 2-arylpropanoic class. A 3,5-dinitro-IBP derivative was found to be more potent than IBP but equally selective. Other synthetic derivatives of IBP were less active, and the free carboxylic acid of IBP seems to be essential for its anti-TB activity. IBP, carprofen and the 3,5-dinitro-IBP derivative exhibited activity against multidrug-resistant isolates and stationary phase bacilli. On the basis of the human targets of the 2-arylpropanoic analgesics, the protein initiation factor infB (Rv2839c) of M tuberculosis was proposed as a potential molecular target.ConclusionsThe HT-SPOTi method can be employed reliably and reproducibly to screen the antimicrobial potency of different compounds. IBP demonstrated specific antitubercular activity, while carprofen was the most selective agent among the 2-arylpropanoic class. Activity against stationary phase bacilli and multidrug-resistant isolates permits us to speculate a novel mechanism of antimycobacterial action. Further medicinal chemistry and target elucidation studies could potentially lead to new therapies against TB.

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Section: Discussionmentioning

confidence: 99%

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay

et al. 2013

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“…Our results correspond with their study, as we also did not find any change of this parameter in pigs after administration of carprofen or meloxicam. Unlike McKellar, we were not able to monitor values of thromboxane B2 as an indicator of COX activity of platelets (McKellar et al 1990(McKellar et al , 1994. We also did not detect significant APTT and PT deviations in control animals after administration of carprofen or meloxicam.…”

Section: Discussionmentioning

confidence: 82%

“…Buccal mucosal bleeding time and clotting ability (McKellar et al 1990) were not affected by administration of carprofen. McKellar et al (1990McKellar et al ( , 1994 monitored thromboxane B2 as an indicator of COX activity of platelets and found that in vitro administration of carprofen did not impair the platelets' production of thromboxane B2.…”

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confidence: 99%

Effects of carprofen or meloxicam on selected haemostatic variables in miniature pigs after orthopaedic surgery

et al. 2011

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The aim of the study was to detect and compare the haemostatic variables and bleeding after 7‑days administration of carprofen or meloxicam in clinically healthy miniature pigs. Twenty-one clinically healthy Göttingen miniature pigs were divided into 3 groups. Selected haemostatic variables such as platelet count, prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, serum biochemical variables such as total protein, bilirubin, urea, creatinine, alkaline phosphatase, alanine aminotransferase and gamma-glutamyltransferase and haemoglobin, haematocrit, red blood cells, white blood cells and buccal mucosal bleeding time were assessed before and 7 days after daily intramuscular administration of saline (1.5 ml per animal, control group), carprofen (2 mg·kg-1) or meloxicam (0.1 mg·kg-1). In pigs receiving carprofen or meloxicam, the thrombin time was significantly increased (p< 0.01) compared to the control group. In animals receiving carprofen, serum urea and creatinine were significantly decreased, compared to the control (p< 0.01) or meloxicam (p< 0.05) groups. In pigs receiving meloxicam, serum urea was significantly decreased (p< 0.05) compared to the control group. Significant differences were not detected in other haemostatic, biochemical variables or bleeding time compared to other groups or to the pretreatment values. Intramuscular administration of carprofen or meloxicam in healthy miniature pigs for 7 days causes sporadic, but not clinically important changes of selected haemostatic variables. Therefore, we can recommend them for perioperative use, e.g. for their analgesic effects, in orthopaedic or other surgical procedures without increased bleeding.

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“…Karprofen derişiminin 1-10 g / ml arasında olmasının ise, kıkırdak matriks bütünlüğünün korunmasında ve kıkırdak proteoglikan yıkımına herhangi bir dolaysız etkisi olmadan, seçici bir şekilde, yeni kıkırdak GAG sentezini uyararak potansiyel yararlı bir etki sağladığı görülmüştür. 24,37 . …”

Section: Tablo 4 Tetrasiklinlerin Etkileri 15unclassified

The role of matrix metalloproteinases in canine joint diseases and treatment approaches

Hişmioğulları¹,

Hişmioğulları²

2014

BSBD

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bsbd@balikesir.edu.tr www.bau-sbdergisi.com ÖZET Eklem hastalıklarında karşılaşılan kıkırdak ve kemik doku yıkımlanmasından sorumlu başlıca maddeler; kollajen ve proteoglikanı yıkımlayan proteinazlardır. Proteolitik enzimlerin 4 ana sınıfı olan aspartik proteinazlar, sistein proteinazlar, serin proteinazlar ve metalloproteinazlar destek dokunun hem normal hareketinde, hem de patolojik yıkımında iş görürler. Bu proteinazlar, eklem içinde farklı hücreler tarafından hazırlanırlar. Her bir enzim, etkilerini durduran, özel protein benzeri inhibitörler tarafından inhibe edilebilir. Son araştırmalar, matriks metalloproteinazlarının eklem hastalıklarındaki birçok sürece karıştığına işaret etmektedirler. Eklem yangılarında (artritis) kıkırdak ve kemiğin yıkımlanması, eklemi normal bir şekilde işlev görmekten alıkoymaktadır. Birçok olayda, eklem yüzeyinin geniş bir bölümü ile birlikte, bu kısmın altındaki kemik de zarar görmüştür. Geleneksel tedaviler, bu hastalığın altında yatan süreçlere çok az etki ederler ve son zamanlarda, proteinaz inhibitörlerinin kullanımı, yeni bir terapötik yaklaşım olarak önerilmektedir. Proteinaz inhibitörleri, model sistemlerde, hastanın kıkırdak yıkımını önleyebilir ve gelecekteki deneysel çalışmalar, bu maddelerin in vivo etkinliklerini ortaya koyabilecektir. Anahtar Kelimeler: Matriks metalloproteinazları, Artritis, Proteinazlar SUMMARYProteinases that degrade collagen and proteoglycan are mainly responsible for disintegration of cartilage and bone in joint diseases. Four major classes of proteolytic enzymes which aspartic proteinases, cysteine proteinases, serine proteinases and metalloproteinases perform in normal functioning of connective tissue as well as its pathological destruction. These proteinases prepared by different cells within the joint. Each enzyme may be inhibited by specific protein-like inhibitors which block its effect. The recent research indicate that matrix metalloproteinases involved in many processes in joint diseases. In joint inflammation (arthritis), the degradation of cartilage and bone prevented the joint from functioning in a normal way. In many cases, the large portion of articular surface with underneath bone damaged as well. Conventional therapies have little effect on the underlying processes of this diseases and recently, the use of protease inhibitors proposed as a novel therapeutic approach. In model systems, proteinase inhibitors could prevent cartilage damage in patients and future experimental studies may reveal in vivo activities of these substances.

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Stereospecific pharmacodynamics and pharmacokinetics of carprofen in the dog

Cited by 82 publications

References 16 publications

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay

Effects of carprofen or meloxicam on selected haemostatic variables in miniature pigs after orthopaedic surgery

The role of matrix metalloproteinases in canine joint diseases and treatment approaches

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