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Compartment Models

Compartment Models. Touqeer Ahmed Ph.D. Atta- ur - Rahman School of Applied Bioscience, National University of Sciences and Technology 21 st October, 2013. Introduction to Compartment Models.

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Compartment Models

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  1. Compartment Models Touqeer Ahmed Ph.D. Atta-ur-Rahman School of Applied Bioscience, National University of Sciences and Technology 21st October, 2013

  2. Introduction to Compartment Models • A model is a hypothesis, using mathematical terms to describe quantitative relationships concisely. • Pharmacokinetic models are relatively simple mathematical schemes that represent complex physiologic spaces or processes. Accurate modeling is important for precise determination of elimination rate Uses • Predict plasma, tissues and urine levels with dosage regimen • Calculation of the optimum dosage regimen for the patients • Estimate the possible accumulation of the drug and its metabolites • Correlate the drug concentration with the pharmacologic/toxicologic response • Evaluate differences between the rate and availability of the drugs • Describe the changes in the absorption during the disease state • Explain drug interactions

  3. Calculations and Considerations • X and Y axis • Variables (independent and dependent) • Standard way is to plot independent variable on the X axis and dependent variable on the Y axis • Graphs (why straight line is important?) • (because it helps us predict values for which there is no experimental observations are present) • Slope • Slope = y2 – y1 /x2 –x1 • Rate of the reactions • Zero order and first order reactions • Half life • t1/2

  4. Units in Pharmacokinetics

  5. Types of Pharmacokinetic Compartment Models 1. Mammillary models (most commonly used) • Important characteristic is that the elimination of the drug is from the central compartment 2. Catenary model (since, like a train of the compartments, thats why rarely used) 3. Physiologic models (Flow model) • Based on the known anatomic and physiologic data • No curve data fitting is required • The tissue size, blood flow to the tissues may vary in the pathophysiologic conditions • Can be applied to the several species as the organs and their blood flow may not vary as much

  6. Compartment Models One compartment Model Two compartment Model

  7. One Compartment Model • Compartment Model • Elimination rate constant Equation Example Page number 46-47 • Apparent Volume of distribution • Equation • Its significance • Clearance If dose is 100 mg dissolved in 10 ml and the 10 mg eliminated per min then • Amount per unit time (10mg/min) –for the zero order • Volume per unit time (1 ml/min) – for the first order • Fraction per unit time (1/10 per min) – PKs take it as first order

  8. Two Compartment Models Central compartment (highly perfused tissues): Heart, brain, hepatic portal system, kidney, skin muscles Peripheral compartment (slowly perfused tissues): Bone, ligament, tendons, cartilage and teeth e.g. Isotretinoin and colchicine studied in two compartment models Aminophylline (IV) follows this model K12 Central compartment Peripheral compartment K21 Characteristic bi-exponential curve K10 Distribution and elimination • Reason for the bi-exponential curve-Figure number 4.3 • Method of residual-Figure number 4.4 • -Table number 4.3

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