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    Add as FriendExtra vascular two compartment unchanged drug in blood/plasma

    by: Arun

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    1 : Extravascular Two-Compartment Model Unchanged Drug In Blood/Plasma
    2 : Two-Compartment Open Model: 1. Central compartment: Comprises of blood and highly per fused tissues like lungs, liver, kidneys, etc., that equilibrate with the drug rapidly. Elimination usually occurs from this compartment. 2. Peripheral compartment: Comprising of poorly per fused and slow equilibrating tissues such as muscles, skin, adipose, etc., and considered as hybrid of several functional physiological units.
    3 : Two-Compartment Types: Depending on the drug elimination there are three types of two-compartment models Are categorized, 1. Two-compartment with elimination from central compartment. 2. Two-compartment with elimination from peripheral compartment. 3. Two-compartment with elimination from both the compartments.
    4 : Advantages Of Compartment Models: It is a simple and flexible approach. Visual representation of various rate processes involved in drug disposition. It shows how many rate constants are necessary to describe these processes. It is useful in predicting drug concentration-time profile in both normal physiologic and in pathologic conditions. It is important in the development of dosage regimens.
    5 : Disadvantages Of Compartment Models: No relationship with the physiologic functions or the anatomic structure of the species. Extensive efforts are required in the development of an exact model The model is based on curve fitting of plasma concentration with complex multi exponential mathematical equations. The model may vary within a study population. Compartment model may change with route of administration Difficulties generally arise when using model to interpret the differences between results from human and animal experiments.
    6 : Basic consideration in developing a two-compartment model: In this model, the drug distributes into two compartments, the central compartment and the Peripheral compartment. 2. The drug distribution and elimination are assumed to take place by first order kinetics. 3. The concentration of drug in a compartment is assumed to be uniform in its volume Of distribution. 4. The three types of drug elimination are also taken into consideration but as the drug elimination is presumed to from the central compartment as major sites of drug Elimination occur in organs such as kidney and liver. However, other models may be used if information about the drug elimination is known.
    7 : 1 Central Compartment 2 Peripheral Compartment K12 K21 Extravascular Two-Compartment Open Model: Ka K10
    8 : Rate of change of amount of = - K12.A1 - K10.A1 + K21.A2 drug in compartment 1 Rate of movement Rate of Rate of movement from compartment 1 Elimination from compartment 2 to compartment 2 to compartment 1 Rate of change of amount of = K12.A1 - K21.A2 drug in compartment 2 Rate of movement Rate of movement from compartment 1 from compartment 2 to compartment 2 to compartment 1 (Where A1 and A2 are the amount of drug in compartment 1 and 2, respectively)
    9 : Distribution Function For Central Compartment: S + E2 ds,c = (S+E1) (S+E2) - K12 K21 where E1 = k10 + k12 and E2 = k21. The constant k10 is the apparent first-order elimination rate constant from the central compartment and k12 and k21 are the inter compartmental transfer rate constants. Expansion of the denominators, when n=2 yields S + E2 ds,c = S2 + S (E1+E2) + E1E2 - K12K21 S + E2 ds,c = S2 + S (?1+?2) + ?1?2
    10 : By comparing it can be shown that, ?l + ?2 = El + E2 and ?1?2 = E1E2 - k12 k21. Substitution of k10 + k12 for E1 and k21 for E2 yields the following equations for ?1 and ?2 (distribution constants), ? l + ? 2 = k10 + k 12 + k 21 and ? 1?2 = k10 k21 ?l is by definition greater than ?2. The specific equation that describes the Bi exponential decay in plasma concentrations of a drug can be readily obtained by setting n = 2, C = A1e - ?1t + A2e – ?2t
    11 : where Al and A2 are given by, X0 (E2- ?1) X0 (k21- ?1) A1 = = Vc (?2- ?1) Vc (?2- ?1) and X0 (E2- ?2) X0 (k21- ?2) A2 = = Vc (?1- ?2) Vc (?1- ?2) The terms ?1, ?2, A1 and A2 are commonly referred to as a, ß, A and B in the literature. Once these parameters are determined, the constants k10, k12 and k21 can be calculated. The apparent volume of the central compartment, Vc is X0 Vc = A1+A2
    12 : Substitution of Al + A2 for XO / Vc (A1+A2) (k21- ?2) A2 = ?1- ?2 which can be solved for k21, since A1 ?2 + A2 ?1 k21 = A1+A2 The elimination rate constant from the central compartment can now be calculated since k21 is known and ?1 ?2 = k10 k21 ?1 ?2 k10 = k21 Recalling that ?l + ?2 = k10 + k12 + k21, k 12 = ? l + ? 2 - k21 - k l 0
    13 : Calculation Of Area Under Curve (AUC): Or in simple form it can be calculated as, Area of trapezium = Area of triangle + Area of rectangle (1/2*base*height) (length*breadth)
    14 : References: 1. Brahmankar D.M., Jaiswal S.B., Biopharmaceutics and Pharmacokinetics – A treatise, 2nd edition Vallabh Prakashan, Delhi 2009 2. Milo Gibaldi., Donald Perrier., Pharmacokinetics, Volume 15, 2nd edition, 2007 3. Venkateswarlu.V., Biopharmaceutics and Pharmacokinetics.

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