Term
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Definition
| the study of the modeling and mathematical description of the time course of dispersion of xenobiotics |
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Term
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Definition
| the rate of chemical elimination from the body in terms of the volume of fluid containing chemical that is cleared per unit time |
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Term
| What does a high clearance value mean? |
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Definition
| indicates rapid and efficient removal of chemicals from the body |
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Term
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Definition
| the time required for plasma or blood concentration to decrease by 1/2 |
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Term
| What are the characteristics of half life if a compound is eliminated by 1st order kinetics? |
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Definition
| time required for plasma concentration to decrease is constant * half-life is independent of dose and does not change with increasing dose |
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Term
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Definition
| the removal of a chemical from the body - this includes biotransformation, exhalation, or excretion |
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Term
| If a chemical follows a 1st order process, what is the rate of elimination proportional to? |
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Definition
| the amount of chemical in the body at that time |
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Term
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Definition
| the fraction of a chemical that reaches the systemic circulation |
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Term
| What are 4 factors that can alter the bioavailability of a chemical? |
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Definition
| limited absorption after oral dosing * intestines may clear some of it in a 1st pass effect * liver may clear some in a 1st pass effect * the mode of formulation |
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Term
| What is the basic difference between a 1 compartment and a 2 compartment model? |
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Definition
| a 1 compartment model assumes that you have iv injection into the central compartment (plasma) and that this equilibrates very rapidly with the tissues and views the body as a homogeneous unit, a 2 compartment model assumes that chemicals require a longer time for tissue and plasma concentrations to eqilibrate - there is more than one dispositional phase |
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Term
| What is the physiological rather than the classic model have a lot more predictive power? |
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Definition
| the constants in the classic model are based solely on data - the physiological constants are based on known or hypothesized biological processes and can be extrapolated from observed to predictive - you can apply these processes to other species and use the same model to predict what will happen in other species - it's also a lot more flexible - you can find the distribution to any organ or tissue, it will handle complex dosing regimens |
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Term
| What are some advantages to physiological modeling? |
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Definition
| it provides a time course of distribution to any organ or tissue * it allows for estimation of the effects of changing physiological parameters on tissues * the same model can be used to predict effects in multiple species * complex dosing schedules can be accomodated |
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Term
| What is a physiologic compartment? |
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Definition
| a single region of the body with a uniform xenobiotic distribution - can be a portion of an organ or a single blood vessel, the entire organ, or a widely distributed tissue type like fat |
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Term
| What are the 3 subcompartments in a physiologic model? |
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Definition
| vascular space - it is through this that the compartment is perfused with blood * interstitial space - forms the matrix for the cells * intracellular space - within the cells |
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Term
| What are the basic differences between classic and physiologic models of toxicokinetics? |
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Definition
| in classic, all the rate constants are based on data, in physiologic, the rate constants represent a measurable process - also in classic, the body is viewed as a homogenious unit, but in physiologic, you can get very specific and predict distribution in any organ or tissue taking into account the various characteristics of that organ or tissue |
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Term
| What does perfusion limited mean? |
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Definition
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Term
| In perfusion limited tissues, what is the rate of xenobiotic uptake limited by? |
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Definition
| the rate blood arrives at the tissue - not at the rate it crosses the membrane |
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Term
| What are the compartments in capillaries? What is the exception? |
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Definition
| extracellular space - the vascular and interstitial spaces are combined b/c they are in equilibrium - the exception is the brain - capillaries there are tight and the intracellular space - in perfusion limited compartmentsthe extracellular and intracellular are presumed to be in equilibrium |
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Term
| What does diffusion limited mean? |
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Definition
| the blood flow rate is fast, but diffusion across the membrane is slow - the flux between extracellular and intracellular compartments is low |
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Term
| What does diffusion limitation depend on? |
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Definition
| cell membrane permeability and total membrane area |
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Term
| What are the 2 assumptions in classic toxicokinetics? |
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Definition
| the concentration of the compound in the blood/plasma is in equilibrium in tissues * the central compartment contains rapidly perfused tissues capable of eliminating the chemical -kidney and liver |
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Term
| What are the advantages of classic toxicokinetics? |
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Definition
| requires no info about tissue physiology or anatomical structure * can predict plasma concentration at different doses* can est. a time course of chemical in plasma and tissues * can determine the effective dose and dose regimens i tox studies |
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Term
| What does the volume of distribution relate? |
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Definition
| the total amount of chemical to the concentration of xenobiotic in plasma |
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Term
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Definition
| the apparent Vd - the concentration of chemical in plasma at time 0 - have to extrapolate the curve |
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Term
| What are the assumptions with the lung? |
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Definition
| ventilation is continuous * the lung is not a separate compartment - it's a conductor b/c everything that goes into the lungs goes into arterial blood * vapor in alveolar air and arterial blood in the lungs are in rapid equilibrium * diffusion is perfusion limited |
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Term
| What is special about the liver as a compartment? |
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Definition
| it is a separate compartment * flow limited (perfusion) but it has an additional process for metabolic elimination |
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Term
| What is special about blood? |
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Definition
| links tissue compartments * not a compartment itself unless blood cells are a target * a tissue receives xenobiotic via arterial blood, except in the liver (arterial and portal blood) and heart (mixed venous blood) |
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