lec 4 IntestinalTransportPt1sm

lec 4 IntestinalTransportPt1sm - NS120 -Molecular...

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1 NS120 -Molecular Toxicology Molecular mechanisms of toxicant absorption and efflux by the intestine Learning Objectives Define attributes of xenobiotics that determines their ability to be transported across membranes. Name GI factors that affect xenobiotic absorption. What evidence exists to suggest that other mechanisms besides passive diffusion of non-ionized forms are present to transport xenobiotics? Describe two models used to determine how a xenobiotic is transported from the intestine. Describe the role of oligopeptide transporters in xenobiotic uptake
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2 Readings Carrier Mediated Intestinal Transport of Drugs , Pharmaceutical Research, Vol. 13, 963-977, 1996 ABC of Oral Bioavailability: Transporters as Gatekeepers in the Gut. Gut 2003;52:1788–1795 Transport of Peptidomimetic Drugs by the Intestinal Di/tri-peptide Transporter, PepT1 Toxicology 2002, 90, 285–296. Role of metabolic enzymes and efflux transporters in the absorption of drugs from the small intestine European Journal of Pharmaceutical Sciences 12 (2000) 3–12 • A bsorption • D istribution • M etabolism • E xcretion •ABSORPTION: Transport of a xenobiotic FROM the site of administration/exposure INTO plasma . •DISTRIBUTION: Transport of xenobiotic within the body •METABOLISM: Biotransformation of drugs/pollutants. •EXCRETION: Removal of chemical and their metabolites from the body. •DISPOSITION- absorption, distribution, biotransformation, and excretion •TOXICOKINETICS - the quantitation and determination of the time course of disposition •TARGET - site where xenobiotic produces damage.
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3 Absorption: Toxicant enters blood Inhalation--readily absorb gases into the blood stream Inhalation--readily absorb gases into the blood stream via the alveoli. (Large alveolar surface, high blood flow, via the alveoli. (Large alveolar surface, high blood flow, and proximity of blood to alveolar air) and proximity of blood to alveolar air) Ingestion--absorption through GI tract- stomach and
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lec 4 IntestinalTransportPt1sm - NS120 -Molecular...

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