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    Anatomical and physiological differences between various species used in studies on the pharmacokinetics and toxicology of xenobiotics. A review of literature

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    Authors
    Zwart LL de
    Rompelberg CJM
    Sips AJAM
    Welink J
    Engelen JGM van
    Series/Report no.
    RIVM Rapport 623860010
    Language
    en
    
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    Title
    Anatomical and physiological differences between various species used in studies on the pharmacokinetics and toxicology of xenobiotics. A review of literature
    Translated Title
    Anatomische en fysiologische verschillen tussen species gebruikt in studies naar farmacokinetiek en toxicologie van xenobiotica. Een literatuur overzicht
    Publiekssamenvatting
    This is the first report of the project 'Selection of species and interspecies differences in relation to kinetics and dynamics of compounds'. An inventory was made of relevant physiological and anatomical characteristics of various species most commonly used in studies on pharmacokinetics and toxicology of oral exposure to xenobiotics. The species studied were: the human, mouse, rat, rabbit, dog, (mini)pig and monkey. The anatomical and physiological characteristics of the different compartments of the gastrointestinal tract, mouth, stomach and small intestine, and of the bile and metabolism in liver and small intestine were reviewed. This report is primarily meant as a review for researchers using animal models to study pharmacokinetics and toxicokinetics of xenobiotics, and for risk assessors on pharmacokinetics and toxicokinetics. The aim of the project is to gain insight into the consequences of interspecies differences in anatomy and physiology on the pharmacokinetics of various classes of compounds. In future, this should lead to improved species selection and subsequently to improved animal-human extrapolation.
    Dit is het eerste rapport binnen het (deel)project getiteld 'Specieskeuze en interspecies verschillen in relatie tot kinetiek en dynamie van stoffen'. In dit rapport zijn relevante fysiologische en anatomische eigenschappen ge6nventariseerd van diersoorten die het meest gebruikt worden tijdens onderzoek naar de farmacokinetiek en toxicologische effecten van oraal toegediende xenobiotica. De volgende diersoorten zijn bestudeerd: mens, muis, rat, konijn, hond, varken, minipig en aap. Voor elke diersoort zijn de anatomische en fysiologische eigenschappen van de verschillende compartimenten van het maag-darm kanaal: mond, maag, dunne darm, gal alsmede van het metabolisme in de lever en dunne darm beschreven. Dit rapport is bedoeld overzicht te geven over interspecies-verschillen voor onderzoekers betrokken bij het opstellen van risico evaluaties van stoffen en voor onderzoekers die diermodellen gebruiken tijdens de studie naar de farmacokinetiek en toxicokinetiek van xenobiotica. Het doel van dit project is om inzicht te krijgen in de consequenties van anatomische en fysiologische verschillen tussen species voor de kinetiek van verschillende soorten verbindingen. Deze informatie moet leiden tot een verbeterde species selectie en vervolgens tot een verbeterde dier-mens extrapolatie.
    Publisher
    Rijksinstituut voor Volksgezondheid en Milieu RIVM
    URI
    http://hdl.handle.net/10029/10210
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    RIVM official reports

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