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Handbook of Experimental Pharmacology Volume 199 Editor-in-Chief F.B.Hofmann,München EditorialBoard J.A.Beavo,Seattle,WA A.Busch,Berlin D.Ganten,Berlin J.-A.Karlsson,Singapore M.C.Michel,Amsterdam C.P.Page,London W.Rosenthal,Berlin Forfurthervolumes: http://www.springer.com/series/164 Fiona Cunningham Jonathan Elliott Peter Lees l l Editors Comparative and Veterinary Pharmacology Editors FionaCunningham JonathanElliott RoyalVeterinaryCollege RoyalVeterinaryCollege Dept.VeterinaryBasic Dept.VeterinaryBasicSciences Sciences RoyalCollegeStreet HawksheadLane LondonNW1OTU,UK Hertfordshire [email protected] UnitedKingdomAL97TA [email protected] PeterLees RoyalVeterinaryCollege Dept.VeterinaryBasic Sciences HawksheadLane Hertfordshire UnitedKingdomAL97TA [email protected] ISSN0171-2004 e-ISSN1865-0325 ISBN978-3-642-10323-0 e-ISBN978-3-642-10324-7 DOI10.1007/978-3-642-10324-7 SpringerHeidelbergDordrechtLondonNewYork LibraryofCongressControlNumber:2010920286 #Springer-VerlagBerlinHeidelberg2010 Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthematerialis concerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broadcasting, reproductiononmicrofilmorinanyotherway,andstorageindatabanks.Duplicationofthispublication orpartsthereofispermittedonlyundertheprovisionsoftheGermanCopyrightLawofSeptember9, 1965,initscurrentversion,andpermissionforusemustalwaysbeobtainedfromSpringer.Violations areliabletoprosecutionundertheGermanCopyrightLaw. Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoesnot imply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevantprotec- tivelawsandregulationsandthereforefreeforgeneraluse. Coverdesign:SPiPublisherServices Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Thehuman–animalbondhasevolvedanddiversifieddowntheages.Dogs,catsand even horses, have long fulfilled the role of faithful companion and indeed, as exemplifiedbytheintroductionofseeingandhearingdogs,theremaybeacritical levelofco-dependencybetweenthespecies.Inthetwenty-firstcentury,theanimal types that are kept as pets in many parts of the world are extensive ranging from reptiles through rodents to ruminants and beyond. As would be predicted by the natureoftherelationship,theapproachtotreatmentofacompanionanimalisoften closelyalignedtothatwhichwouldhavebeenofferedtotheirowner.However,an increasingawarenessofwelfareissues,suchastherecognitionthatanimalsexperi- encepainandtheprovenbenefitsofdiseasepreventioninintensivefarmingunits, togetherwiththegrowthinzoosandwildlifeparks,hasincreasedthelikelihoodof foodproducingandnon-domesticatedanimalsreceivingmedicinalproductsduring theirlife-time. Although many of the individual drugs or classes of drugs administered to animalsarethesameas,orderivedfrom,thosegiventoman,thesafeandeffective useofdrugsinanimalsoftencannotbeachievedbysimplytransposingknowledge ofdrugactionon,orbehaviourin,thebodyfromonespeciestoanother.Theimpact of the anatomical, physiological and pathophysiological variability that spans the animal kingdom can often profoundly alter drug response. Thus the discipline of veterinarypharmacology,whichhasgrownupalongsideanddevelopedfrombasic andmedicalpharmacology,hasdrawnfromandbuiltupon,buthassometimeshad tomarkedlyadaptdataobtainedfromdruguseforthepreventionandtreatmentof diseaseinman.Incompilingthisvolume,SpringerVerlaghasprovideduswiththe opportunitytocollaboratewithworldexpertsinthisfieldinordertobringtogether a series of succinct overviews in some key areas of veterinary pharmacology and therapeutics. Those topics addressed in the first part of the volume (Chaps. 1–7) illustrate both the commonality and differences between drug pharmacodynamics and pharmacokinetics in animals and man, looking also to the future benefits that introductionofnewtechnologiesmaybring.Thoseinthelatterpart(Chaps.8–12) demonstrate the potential impact of drug use in animals on man and the v vi Preface environment,aswellaspresentingthemanybenefitstomanbroughtaboutbythe geneticmodificationofanimals. Wehopethatyouwillenjoyreadingthisvolumeasmuchaswe,theeditors,have enjoyedourroleinitscreation. October2009 FionaCunningham JonathanElliott PeterLees Contents PartI TopicsinVeterinaryPharmacology Introduction .................................................................. 3 FionaCunningham,JonathanElliott,andPeterLees SpeciesDifferencesinPharmacokinetics andPharmacodynamics ..................................................... 19 Pierre-LouisToutain,AudeFerran,andAlainBousquet-Me´lou ComparativeandVeterinaryPharmacogenomics ......................... 49 CarrieM.MosherandMichaelH.Court DrugDeliverySystemsinDomesticAnimalSpecies ...................... 79 DavidJ.Brayden,EmilieM.Oudot,andAlanW.Baird PopulationMedicineandControlofEpidemics ........................... 113 HafidBenchaoui InterspeciesAllometricScaling ............................................. 139 RobertP.Hunter PainandAnalgesiainDomesticAnimals .................................. 159 AlexLivingston NewTechnologiesforApplicationtoVeterinaryTherapeutics .......... 191 JimE.Riviere vii viii Contents PartII TheInterfaceofVeterinaryPharmacologyandMan GeneticallyModifiedAnimalsandPharmacologicalResearch ........... 213 DominicJ.Wells AntimicrobialDrugResistance ............................................. 227 MarilynMartinezandPeterSilley DrugResidues ................................................................ 265 PhilipT.Reeves VeterinaryMedicinesandtheEnvironment ............................... 291 AlistairB.A.Boxall VeterinaryMedicinesandCompetitionAnimals:TheQuestion ofMedicationVersusDopingControl ...................................... 315 Pierre-LouisToutain Index .......................................................................... 341 Contributors Alan W. Baird School of Agriculture, Food Science and Veterinary Medicine, UniversityCollegeDublinandUCDConwayInstitute,Belfield,Dublin4,Ireland, [email protected] Hafid Benchaoui Novartis Animal Health, Research & Development, Schwarz- waldallee 215, WRO-1032.2.44, CH-4002, Basel, Switzerland, hafid.benchaoui@ novartis.com AlainBousquet-Me´lou Unite´ MixtedeRecherche181PhysiopathologieetTox- icologieExpe´rimentales,InstitutNationaldelaRechercheAgronomiqueet,Ecole Nationale Ve´te´rinaire de Toulouse,23 ChemindesCapelles, BP 87 614, F-31076 Toulousecedex3,France,[email protected] Alistair B.A. Boxall Environment Department, University of York, Heslington, York,YO105DD,UK,[email protected] DavidJ.Brayden SchoolofAgriculture,FoodScienceandVeterinaryMedicine, University College Dublin and UCD Conway Institute, Belfield, Dublin 4, Ireland,[email protected] MichaelH.Court DepartmentofPharmacologyandExperimentalTherapeutics, Tufts University, School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA,[email protected] FionaCunningham DepartmentofVeterinaryBasicSciences,RoyalVeterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK, [email protected] Jonathan Elliott Department of Veterinary Basic Sciences, Royal Veterinary College,RoyalCollegeStreet,LondonNW1OTU,UK,[email protected] ix x Contributors Aude Ferran Unite´ Mixte de Recherche 181 Physiopathologie et Toxicologie Expe´rimentales,InstitutNationaldelaRechercheAgronomiqueetEcoleNationale Ve´te´rinaire de Toulouse, 23 Chemin des Capelles, BP 87 614, 31076 Toulouse cedex03,France,[email protected] RobertP.Hunter ElancoAnimalHealth,2001WestMainStreet,DropCodeGL 36,Greenfield,IN46140,USA,[email protected] Peter Lees Department of Veterinary Basic Sciences, Royal Veterinary College, HawksheadLane,NorthMymms,HertfordshireAL97TA,UK,[email protected] Alex Livingston Department of Veterinary Biomedical Sciences, Veterinary Medicine Building, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan,Canada,S7N5B4,[email protected] Marilyn Martinez Office of New Animal Drug Evaluation (HFV-130), Center for Veterinary Medicine Food and Drug Administration, 7500 Standish Place, Rockville,MD20855,USA,[email protected] Carrie M. Mosher Department of Pharmacology and Experimental Therapeutics, TuftsUniversitySchoolofMedicine,136HarrisonAvenue,Boston,MA02111,USA EmilieM.Oudot SchoolofAgriculture,FoodScienceandVeterinaryMedicine, UniversityCollege,DublinandUCDConwayInstitute,Belfield,Dublin4,Ireland, [email protected] Philip T. Reeves Australian Pesticides and Veterinary Medicines Authority, POBox6182,KingstonACT2604,Australia,[email protected] Jim E. Riviere Center for Chemical Toxicology Research and Pharmacokinetics, DepartmentofPopulationHealthandPathobiology,CollegeofVeterinaryMedicine, NorthCarolinaStateUniversity,Raleigh,NC27606,USA,[email protected] Peter Silley Consult Limited, Enterprise House, Ocean Village, Southampton, Hampshire,SO143XB,UK,[email protected] Pierre-Louis Toutain Unite´ Mixte de Recherche 181 Physiopathologie et Tox- icologieExpe´rimentales, Institut Nationalde la Recherche Agronomique etEcole Nationale Ve´te´rinaire de Toulouse, 23 Chemin des Capelles, BP 87 614, 31076 Toulousecedex03,France,[email protected] Dominic J. Wells Department of Veterinary Basic Sciences, Royal Veterinary College,LondonNW1OTU,[email protected]