Sperimentazione nel coniglio

Il presente studio mostra come i parametri farmacocinetici del grapiprant dopo somministrazione IV alla dose di 2 mg/kg nel coniglio siano simili a quelli rilevati nello studio precedente nel cane.

Inoltre mostra che l'effetto antinocicettivo del grapiprant insorge ad 1 h e dura fino a 10 h dalla somministrazione del farmaco, ma mostra anche una massima antinocicezione (4-8 h) non significativamente differente rispetto a quella del meloxicam. Quindi grapiprant sembra essere un'ottima opzione per l'antinocicezione nel coniglio ma studi con somministrazioni di diverse dosi e vie di somministrazione sono necessari per valutare il regime di dosaggio nei conigli.

66

67 Anonymous (1986).

http://www.salute.gov.it/portale/temi/p2_6.jsp?id=3769&area=curePalliativeTerapiaDolore& menu=terapia (ultimo accesso 14 Febbraio 2017). IASP (International Association for the Study of Pain)

Anonymous (2016). Freedom of information summary. Original new animal drug application, NADA 141-455.

http://www.fda.gov/downloads/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/F OIADrugSummaries/UCM494127.pdf (ultimo accesso 14 Febbraio 2017). U.S. Food and Drug Administration

Barter L.S. & Kwiatkowski A. (2013) “Thermal threshold testing for evaluation of analgesics in New Zealand white rabbits” Journal of the American Association for Laboratory Animal Science. 52: 44-47

Bourne H.R. & Von Zastrow M. “Recettori dei farmaci e farmacodinamica” in Katzung B.G. “Farmacologia generale e clinica” pag. 22-24. Ed. 6 Piccin, Perugia, Italia; 2005

Campbell D.B. (1990) “The use of kinetic-dynamic interactions in the evaluation of drugs” Psychopharmacology. 100: 433-450

Coleman R.A., Smith W.L. & Narumiya S. (1994) “International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes” Pharmacological Reviews. 46: 205-229

De Vito V., Saba A., Hong-Ki L., Owen H., Poapolathep A. & Giorgi M. (2015) “Detection and quantification of the selective EP4 receptor antagonist CJ-023423 (grapiprant) in canine plasma by HPLC with spectrofluorimetric detection”. Journal of Pharmaceutical and Biomedical Analysis. 118: 251-258

Dirig D.M., Salami A., Rathbun M.L., Ozaki G.T. & Yaksh T.L. (1997) “Characterization of variables defining hind paw withdeawal latency evoked by radiant thermal stimuli” Journal of Neuroscience Methods. 76: 183-191

Dong H., Sun H., Magal E., Ding X., Kumar G.N., Chen J.J., Johnson E.J. & Manning B.H. (2008) “Inflammatory pain in the rabbit: a new, efficient method for measuring mechanical hyperalgesia in the hind paw” Journal of Neuroscience Methods. 168: 76-87.

Fleming G.J. & Robertson S.A. (2012) “Assessments of thermal antinociceptive effects of butorphanol and human observer effect on quantitative evaluation of analgesia in green iguanas (Iguana iguana)” American Journal of Veterinary Research. 73: 1507-1511

Foegh M.L. & Ramwell P.W. “Gli eicosanoidi: prostaglandine, trombossani, leucotrieni ed altri metaboliti dell'acido arachidonico” in Katzung B.G. “Farmacologia generale e clinica” pag. 296-298. Ed. 6 Piccin, Perugia, Italia; 2005

Gabrielsson J. & Weiner D. (Eds.) “Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications” ed 5. Swedish Pharmaceutical Press, Stoccolma, Svezia; 2002

Giorgi M. (2012) “Veterinary pharmacology: is it still pharmacology's cinderella?” Clinical and Experimental Pharmacology. 2: 103

68

Giorgi M., Meizler A. & Mills P.C. (2012) “Pharmacokinetics of the novel atypical opioid tapentadol following oral and intravenous administration in dogs”. Veterinary Journal. 194: 309-313

Giorgi M. & Owen H. (2012) “Flupirtine: a human drug with potential for use in the veterinary field” American Journal of Animal and Veterinary Sciences. 7: 213-217

Giorgi M. & Yun H. (2012) “Pharmacokinetics of mirtazapine and its main metabolites in beagle dogs: a pilot study” Veterinary Journal. 192: 239-241

Grösch S., Niederberger E. & Geisslinger G. (2016) “Investigational drugs targeting the prostaglandin E2 signaling pathway for the treatment of inflammatory pain” Expert Opinion on Investigational Drugs. 26: 51-61

Guzman D.S., Drazenovich T.L., KuKanich B., Olsen G.H., Willits N.H. & Paul-Murphy J.R. (2014) “ Evaluation of thermal antinociceptive effects and pharmacokinetics after intramuscular administration of butorphanol tartrate to American kestrels (Falco sparverius)” American Journal of Veterinary Research. 75: 11-18

Harris L.S. & Pierson A.K. (1964) “Some narcotic antagonists in the benzomorphan series” Journal of Pharmacology and Experimental Therapeutics. 143: 141-148

Henke J. & Erhardt W. “Terapia del dolore negli animali da compagnia” ed. italiana Lachin A. Masson Milano, Italia; 2006

Ichitani Y., Shi T., Haeggstrom J.Z., Samuelsson B. & Hokfelt T. (1997) “Increased levels of cycloxygenase-2 mRNA in the rat spinal cord after peripheral inflammation: an in situ hybridization study” NeuroReport. 8: 2949-2952

Kawabata A. (2011) “Prostaglandin E2 and pain-an update” Biological and Pharmaceutical Bulletin Journal. 34: 1170-1173

Kögel B., Terlinden R. & Schneider J. (2014) “Characterization of tramadol, morphine and tapentadol in an acute pain model Beagle dogs” Veterinary Anesthesia and Analgesia. 41: 297- 304

Kirkby Shaw K., Rausch-Derra L.C. & Rhodes L. (2015) “Grapiprant: an EP4 prostaglandin receptor antagonist and novel Therapy for pain and inflammation” Veterinary Medicine and Science DOI: 10.1002/vms3.13

Kumar R., Keshri U.P. & Sharma J. (2013) “Flupirtine: a mini review” Journal of Drug Delivery & Therapeutics. 3: 113-116

Kuner R. (2010) “Central mechanisms of pathologic pain” Nature Medicine. 16: 1258-1266

Lascelles B.D. & Robertson S.A. (2004) “Use for thermal threshold response to evaluate the antinociceptive effects of butorphanol in cats” America Journal of Veterinary Research. 65: 1085-1089

69

Lavy E., Prise U., Soldani G., Neri D., Brandriss A., Chaimd B. & Giorgi M. (2011) “Pharmacokinetics of methylphenidate after oral administration of immediate and sustained- release preparations in Beagle dogs” Veterinary Journal. 189: 336-340

Lin C.R., Amaya F., Barrett L., Wang H., Takada J., Samada T.A. & Woolf C.J. (2006) “Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity” Journal of Pharmacology and Experimental Therapeutics. 319: 1096-1103

Louizos C., Yáñez J.A., Forrest L. & Davies N.M. (2014) “Understanding the Hysteresis Loop Conundrum in Pharmacokinetic/Pharmacodynamic Relationships” Journal of Pharmacy & Pharmaceutical Sciences. 17: 34-91

Marchetti V., Giorgi M., Fioravanti A., Finotello R., Citi S., Canu B., Orlandi P., Di Desiderio T., Danesi R. & Bocci G. (2012) “First- line metronomic chemotherapy in a metastatic model of spontaneous canine tumors: a pilot study” Invest New Drugs. 30: 1725-1730

Nagahisa A. & Okumura T. (2016) “Pharmacology of grapiprant, a novel EP4 antagonist: receptor binding, efficacy in a rodent post-operative pain model, and a dose estimation for controlling pain in dogs” Journal of Veterinary Pharmacology and Therapeutics DOI: 10.1111/jvp.12349

Nakao K., Murase A., Ohshiro H., Okumura T., Taniguchi K., Murata Y., Masuda M., Kato T., Okumura Y. & Takada J. (2007) “CJ-023,423, a novel, potent and selective prostaglandine EP4 receptor antagonist with antihyperalgesic properties” The Journal of Pharmacology and Experimental Therapeutics. 322: 686-694

Nelson D.L. & Cox M.M. “I principi di biochimica di Lehninger” pag. 426. Ed. 5 Zanichelli, Bologna, Italia; 2010

RaQualia (2007a) “Determination of the dose response relationship of CJ-023423 in the rat carrageenin-induced foot edema model” SR_DB1_CJ-023423_RAT_CFE_1_2007

RaQualia (2007b) “Investigation of the inhibitory effects of CJ-023423 on inflammation and bone destruction in adjuvant-induced arthritis rats” SR_DB1_CJ-023423_AIA_1_2007

Rausch-Derra L.C., Huebner M. & Rhodes L. (2015) “Evaluation of the safety of long-term, daily oral administration of grapiprant, a novel drug for treatment of osteoarthritic pain and inflammation, in healthy dogs” American Journal of Veterinary Research. 76: 853-859

Rausch-Derra L.C., Huebner M., Wofford J. & Rhodes L. (2016a): “A prospective randomized, masked, placebo-controlled multisite clinical study of Grapiprant, an EP4 prostaglandin receptor antagonist (PRA), in dogs with osteoarthritis” Journal of Veterinary Internal Medicine. 30: 756-763

Rausch-Derra L.C., Rhodes L., Freshwater L. & Hawks R. (2016b) “Pharmacokinetic comparison of oral tablet and suspension formulations of grapiprant, a novel therapeutic for the pain and inflammation of osteoarthritis in dogs” Journal of Veterinary Pharmacology and Therapeutics. 39: 566-571

70

Rausch-Derra L.C. & Rhodes L. (2016) “Safety and toxicokinetic profiles associated with daily oral administration of grapiprant, a selective antagonist of the prostaglandin E2 EP4 receptor, to cats” American Journal of Veterinary Research. 77: 688-692

Ren K. & Dubner R. (1999) “Inflammatory models of pain and hyperalgesia” ILAR Journal. 40: 111-118

Simon L.S., Lanza F.L., Lipsky P.E., Hubbard R.C., Talwalker S., Schwartz B.D., Isakson P.C. & Geis G.S. (1998) “Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects” Arthritis Rheumatism. 41: 1591-602.

Sladky K.K., Kinney M.E. & Johnson S.M. (2008) “Analgesic efficacy of butorphanol and morphine in bearded dragons and corn snakes” Journal of the American Veterinary Medical Association. 233: 267-273

Sladky K.K., Kinney M.E. & Johnson S.M. (2009) “Effects of opioid receptor activation on thermal antinociception in red-eared slider turtles (Trachemys scripta)” American Journal of Veterinary Research. 70: 1072-1078

Toutain P.L. & Bousquet-Mélou A. (2004a) “Plasma clearance” Journal of Veterinary Pharmacology and Therapeutics. 27: 415-425

Toutain P.L. & Bousquet-Mélou A. (2004b) “Plasma terminal half-life” Journal of Veterinary Pharmacology and Therapeutics. 27: 427-439

Toutain P.L. & Lees P. (2004) “Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine” Journal of Veterinary Pharmacology and Therapeutics. 27: 467-477

Wagner J.G. “Pharmacokinetics for the Pharmaceutical Scientist” Technomic. Lancaster, UK; 1993

World Health Organization (2013) Pre-stems: Suffixes Used in the Selection of INN.

Zimecki M. (2012) “Potential therapeutic interventions via EP2/EP4 prostaglandin receptors” Postepy Higieny I Medycyny Doswiadczalnej. 66: 287-94

Zizzadoro C. & Belloli C. “Autacoidi dell'infiammazione” in Carli S., Ormas P., Re G. & Soldani G. “Farmacologia veterinaria” pag. 397-405. Idelson-Gnocchi, Napoli, Italia; 2009a Zizzadoro C. & Belloli C. “Farmaci per il controllo dell'infiammazione” in Carli S., Ormas P., Re G. & Soldani G. “Farmacologia veterinaria” pag. 457-463 e 471-473. Idelson-Gnocchi, Napoli, Italia; 2009b