{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T13:11:50Z","timestamp":1778332310776,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Carprofen (CP) is a non-steroidal anti-inflammatory drug (NSAID) frequently used to treat respiratory diseases in numerous small animals, but also in large species. CP is a formidable candidate for further therapeutic research of human inflammatory diseases using the pig as an animal model. However, CP administration in swine is very uncommon and respective pharmacokinetics\/bioavailability studies are scarce. A simultaneous population pharmacokinetic analysis after CP intravenous and intramuscular administrations in pigs has shown high extent and rate of absorption and a similar distribution profile with respect to man and other mammals. However, clearance and half-life values found in swine suggest a slower elimination process than that observed in man and some other animal species. Although not reported in other species, liver and kidney concentrations achieved at 48 h post-intramuscular administration in pigs were ten times lower than those found in plasma. Simulations pointed to 4 mg\/kg every 24 h as the best dosage regimen to achieve similar therapeutic levels to those observed in other animal species. All these findings support the use of pig as an animal model to study the anti-inflammatory effects of CP in humans.<\/jats:p>","DOI":"10.3390\/pharmaceutics14051045","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T05:10:32Z","timestamp":1652332232000},"page":"1045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Swine as the Animal Model for Testing New Formulations of Anti-Inflammatory Drugs: Carprofen Pharmacokinetics and Bioavailability of the Intramuscular Route"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2635-554X","authenticated-orcid":false,"given":"Lidia","family":"G\u00f3mez-Segura","sequence":"first","affiliation":[{"name":"Department of Medicine and Animal Health, Faculty of Veterinary, Autonomous University of Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0849-0492","authenticated-orcid":false,"given":"Antoni","family":"Boix-Monta\u00f1es","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9316-8459","authenticated-orcid":false,"given":"Mireia","family":"Mallandrich","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Parra-Coca","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Zootechnic, Faculty of Agriculture Sciences, University of Applied and Environmental Sciences, Bogota 111166, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9465-0538","authenticated-orcid":false,"given":"Jos\u00e9 L.","family":"Soriano-Ruiz","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-4821","authenticated-orcid":false,"given":"Ana Cristina","family":"Calpena","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1lvaro","family":"Gimeno","sequence":"additional","affiliation":[{"name":"Department of Animal Research, Animal House of Bellvitge, University of Barcelona, CCiT-UB, 08907 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Bellido","sequence":"additional","affiliation":[{"name":"Department of Separative Techniques, Scientific and Technological Centers, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Colom","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1177\/009127008002000507","article-title":"Pharmacokinetic and Clinical Studies of Carprofen in Gout","volume":"20","author":"Perel","year":"1980","journal-title":"J. Clin. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/(SICI)1098-1128(199603)16:2<181::AID-MED3>3.0.CO;2-X","article-title":"Constitutive Cyclooxygenase (COX-1) and Inducible Cyclooxygenase (COX-2): Rationale for Selective Inhibition and Progress to Date","volume":"16","author":"Griswold","year":"1996","journal-title":"Med. Res. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1111\/j.1365-2133.2008.08847.x","article-title":"Occupational carprofen photoallergic contact dermatitis","volume":"159","author":"Kerr","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1124\/pr.56.3.3","article-title":"Cyclooxygenase isozymes: The biology of prostaglandin synthesis and inhibition","volume":"56","author":"Simmons","year":"2004","journal-title":"Pharmacol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1136\/vr.164.14.418","article-title":"Systematic Review of the Management of Canine Osteoarthitis","volume":"164","author":"Sandersoln","year":"2009","journal-title":"Vet. Rec."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1365-2885.2004.00589.x","article-title":"Clinical Efficacy of Carprofen as an Adjunct to the Antibacterial Treatment of Bovine Respiratory Disease","volume":"27","author":"Elitok","year":"2004","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1136\/vr.152.13.392","article-title":"Clinical Efficacy of Flunixin: Carprofen and Ketoprofen as Adjuncts to the an-Tibacterial Treatment of Bovine Respiratory Disease","volume":"152","author":"Lockwood","year":"2003","journal-title":"Vet. Rec."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.3168\/jds.S0022-0302(05)72914-3","article-title":"Effect of Carprofen treatment following experimentally induced Escherichia coli mastitis in primiparous cows","volume":"88","author":"Vangroenweghe","year":"2005","journal-title":"J. Dairy Sci."},{"key":"ref_9","first-page":"539","article-title":"Nonsteroidal Anti-Inflammatory Analgesics in Pain Management in Dogs and Cats","volume":"37","author":"Karol","year":"1996","journal-title":"Can. Vet. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sidler, M., Fouch\u00e9, N., Meth, I., Hahn, F., Rechenberg, B., and Kronen, P.W. (2014). Transcutaneous Treatment with Vetdrop Sustains the Adjacent Cartilage in a Microfracturing Joint Defect Model in Sheep. BMC Vet. Res., 10.","DOI":"10.1186\/s12917-014-0268-6"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1532-950X.2007.00314.x","article-title":"Comparison of Analgesic Efficacy of Preoperative or Postoperative Carprofen with or without Preincisional Mepivacaine Epidural Anesthesia in Canine Pelvic or Femoral Fracture Repair","volume":"36","author":"Bergmann","year":"2007","journal-title":"Vet. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/clpt.1988.135","article-title":"Serum Concentration and Dose-Response Relationships for Carprofen in Rheumatoid Arthritis","volume":"44","author":"Furst","year":"1988","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3109\/03009748309095333","article-title":"A Double Blind Crossover Study of Carprofen and Indomethacin in Patients with Rheumatoid Arthritis","volume":"12","author":"Jalava","year":"1983","journal-title":"Scand. J. Rheumatol."},{"key":"ref_14","first-page":"536","article-title":"Double-Blind Comparative Clinical Trial of Carprofen versus Diclofenac-Na in Patients with Coxarthrosis","volume":"5","author":"Knusel","year":"1982","journal-title":"Eur. J. Rheumatol. Inflamm."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gimeno, A., Mestres-Truyol, J., Ojeda-Montes, M.J., Macip, G., Saldivar-Espinoza, B., Cereto-Massagu\u00e9, A., Pujadas, G., and Garcia-Vallv\u00e9, S. (2020). Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113793"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1126\/science.1065199","article-title":"Construction and Analysis of a Human-Chimpanzee Comparative Clone Map","volume":"295","author":"Fujiyama","year":"2002","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lu, M., Zhang, Q., Deng, M., Miao, J., Guo, Y., Gao, W., and Cui, Q. (2008). An analysis of human microRNA and disease associations. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003420"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1046\/j.1365-2885.1999.00202.x","article-title":"Pharmacokinetics of Carprofen Enantiomers in Equine Plasma and Synovial Fluid\u2013A Comparison with Ketoprofen","volume":"22","author":"Armstrong","year":"1992","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1046\/j.1365-2885.2002.00436.x","article-title":"Pharmacodynamics and Enantioselective Pharmacokinetics of Racemic Carprofen in the Horse","volume":"25","author":"Lees","year":"2003","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.2460\/ajvr.2004.65.1479","article-title":"Carprofen after Administration of Racemic Carprofen in Donkeys and Horses","volume":"65","author":"Mealey","year":"2004","journal-title":"Am. J. Vet. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/jvp.12000","article-title":"Influence of Oxytetracycline on Carprofen Pharmacodynamics and Pharmacokinetics in Calves","volume":"36","author":"Brentnall","year":"2013","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.rvsc.2013.01.012","article-title":"Pharmacokinetic\u2013Pharmacodynamic Integration and Modelling of Oxy-Tetracycline Administered Alone and in Combination with Carprofen in Calves","volume":"94","author":"Brentnall","year":"2013","journal-title":"Res. Vet. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1046\/j.1365-2885.2003.00498.x","article-title":"Enantioselective Pharmacokinetics and Cyclo-Oxygenase Inhibition of Carprofen and Carprofen Enantiomers in Sheep","volume":"26","author":"Cheng","year":"2003","journal-title":"J. Vet. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-2885.2008.00975.x","article-title":"Enantioselective Pharmacokinetics of Racemic Carprofen in New Zealand White Rabbits","volume":"31","author":"Hawkins","year":"2008","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/02713680902725962","article-title":"Ocular Pharmacokinetics and Availability of Topically Applied Baicalein in Rabbits","volume":"34","author":"Zhang","year":"2009","journal-title":"Curr. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fourie, T., Cromarty, D., Duncan, N., and Wolter, K.N. (2015). The Safety and Pharmacokinetics of Carprofen, Flunixin and Phenylbutazone in the Cape Vulture (Gyps Coprotheres) Following Oral Exposure. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141419"},{"key":"ref_27","first-page":"492","article-title":"Pharmacokinetic Properties of Carprofen in Humans","volume":"5","author":"Crevoisier","year":"1982","journal-title":"Eur. J. Rheumatol. Inflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1136\/vr.150.22.684","article-title":"Clinical Efficacy and Pharmacokinetics of Carprofen in the Treatment of Dogs with Osteoarthritis","volume":"150","author":"Lipscomb","year":"2002","journal-title":"Vet. Rec."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/jvp.12233","article-title":"Carprofen Pharmacokinetics in Plasma and in Control and Inflamed Canine Tissue Fluid Using in Vivo Ultrafiltration","volume":"39","author":"Messenger","year":"2016","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1046\/j.1365-2885.2000.00253.x","article-title":"The Pharmacokinetics and Effects of Intravenously Adminis-Trated Carprofen and Salicylate on Gastrointestinal Mucosa and Selected Biochemical Measurements in Healthy Cats","volume":"23","author":"Parton","year":"2000","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0034-5288(96)90009-0","article-title":"Phamacodynamics and Enantioselective Pharmacokinetics of Carprofen in the Cat","volume":"60","author":"Taylor","year":"1996","journal-title":"Res. Vet. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.vaa.2020.09.006","article-title":"Pharmacokinetics of Carprofen in Anaesthetized Pigs: A Preliminary Study","volume":"48","author":"Lampreht","year":"2021","journal-title":"Vet. Anaesth. Analg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.4155\/bio.13.73","article-title":"The Advantages of Microflow LC-MS\/MS Compared with Conventional HPLC-MS\/MS for the Analysis of Methotrexate from Human Plasma","volume":"5","author":"Christianson","year":"2013","journal-title":"Bioanalysis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jpha.2016.03.002","article-title":"Development of an LC\u2013MS\/MS Method for the Quantitation of Deoxy-Glycychloxazol in Rat Plasma and Its Application in Pharmacokinetic Study","volume":"6","author":"Li","year":"2016","journal-title":"J. Pharm. Anal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1007\/s00216-012-5860-7","article-title":"Determination of Non-Steroidal an-Ti-Nflammatori Drugs and Theri Metabolitse in Milk by Liquid Chromatrography-Tandem Mass Spectrometry","volume":"403","author":"Jedziniak","year":"2012","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_36","first-page":"414","article-title":"Direct Determination of Diastereomeric Carprofen Glucuronides in Human Plasma and Urine and Preliminary Measurements of Stereoselective Metabolic and Renal Elimination after Oral Administration of Carprofen in Man","volume":"17","author":"Iwakawa","year":"1989","journal-title":"Drug Metab. Dispos."},{"key":"ref_37","unstructured":"FDA (2020, January 10). Bioanalytical Method Validation. Guidance for Industry, Available online: https:\/\/www.fda.gov\/files\/drugs\/published\/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf."},{"key":"ref_38","unstructured":"FDA (2020, January 10). Analytical Procedures and Methods Validation for Drugs and Biologics. Guidance for Industry, Available online: https:\/\/www.fda.gov\/media\/87801\/download."},{"key":"ref_39","unstructured":"(2020, January 10). EMA ICH Q2(R1): Note for Guidance on Validation of Analytical Procedures: Text and Methodology. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-q-2-r1-validation-analytical-procedures-text-methodology-step-5_en.pdf."},{"key":"ref_40","unstructured":"Certara, L.P. Phoenix-64 Build 8.1.0.3530, Certara. Available online: https:\/\/www.certara.com\/."},{"key":"ref_41","unstructured":"Bauer, R.J., and Ludden, T.M. (2009). Improvements and New Estimation Methods in NONMEM 7 for PK\/PD Population Analysis, Icon Development Solutions."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0169-2607(98)00067-4","article-title":"Xpose: An S-PLUS Based Population Pharmacokinetic\/Pharmacodynamic Model Building Aid for NONMEM","volume":"58","author":"Jonsson","year":"1998","journal-title":"Comput. Meth Programs Biomed."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.cmpb.2005.04.005","article-title":"PsN-Toolkit: A Collection of Computer Intensive Statistical Methods for Non-Linear Mixed Effect Modeling Using NONMEM","volume":"79","author":"Lindbom","year":"2005","journal-title":"Comput. Meth Programs Biomed."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/BF01117450","article-title":"Application of Akaike\u2019s Information Criterion (AIC) in the Evalua-Tion of Linear Pharmacokinetics Equations","volume":"6","author":"Yamaoka","year":"1978","journal-title":"J. Pharm. Biopharm"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2133\/dmpk.24.25","article-title":"Mechanistic Basis of Using Body Size and Maturation to Predict Clear-Ance in Humans","volume":"24","author":"Anderson","year":"2009","journal-title":"Drug Metab Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1208\/s12248-009-9133-0","article-title":"Importance of Shrinkage in Empirical Bayes Estimates for Diagnostics: Problems and Solutions","volume":"11","author":"Savic","year":"2009","journal-title":"AAPS J."},{"key":"ref_47","first-page":"1542","article-title":"The Visual Predictive Check Superiority to Standard Diagnostic (Rorschach) Plots","volume":"42","author":"SIM","year":"1963","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1023\/A:1018943613122","article-title":"Physiological Parameters in Laboratory Animals and Humans","volume":"10","author":"Davies","year":"1993","journal-title":"Pharm. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/j.1365-2885.2004.00617.x","article-title":"Pharmacodynamics and Pharmacokinetics of Nonsteroidal Anti-Inflammatory Drugs in Species of Veterinary Interest","volume":"27","author":"Lees","year":"2004","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"20130583","DOI":"10.1098\/rstb.2013.0583","article-title":"Comparative Metabolism as a Key Driver of Wildlife Species Sensitivity to Human and Veterinary Pharmaceuticals","volume":"369","author":"Hutchinson","year":"2014","journal-title":"Phil. Trans. R. Sci. B"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1258\/002367796780739862","article-title":"Simultaneous Measurement of Metabolic Flux in Portally-Drained Viscera, Liver, Spleen, Kidney and Hindquarter in the Conscious Pig","volume":"30","author":"Bostl","year":"1996","journal-title":"Lab. Anim."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/5\/1045\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:09:38Z","timestamp":1760137778000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/5\/1045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,12]]},"references-count":51,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["pharmaceutics14051045"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14051045","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,12]]}}}