Compartment Models PDF

Our bodies composed of what? Intro Compartments considered as what? Body is considered as composed of several compartments that communicate reversibly with each other. A compartment is not a real physiologic or anatomic region, but is considered as a tissue or group of tissues which have similar b...

Our bodies composed of what? Intro Compartments considered as what? Body is considered as composed of several compartments that communicate reversibly with each other. A compartment is not a real physiologic or anatomic region, but is considered as a tissue or group of tissues which have similar blood flow and drug affinity. Simplest Model Predicts the body as single, Feature? kinetically homogenous unit that has no barriers to movement of drug and final distribution equilibrium between drug in plasma and other body fluids is attained instantaneously maintained at all times. Homogenous does not mean equal conc. Instantaneous Distribution Models ( One compartment Open Model) an equilibrium is reached between plasma and various tissues and fluids in the body and any change in plasma conc. can be attributed to elimination of drug from the body rather than uptake by tissues. What does it simply mean? One compartment open model assumes athat any changes that occur in plasma levels of a drug reflect proportional changes in tissue drug levels. Model does not assume that the drug conc. a in plasma is equal to that in other body tissues. Open reflects that the absorption and aelimination are unidirectional and that the drug can be eliminated from the body. 1. One Compartment open model, intravenous adm Various one comp open models based on rate of input as follows: 2. One compartment open model, continuous intravenous infusion 3. One compartment open model , extravascular admn., first order absorption 4. One-compartment open model, extravascular admn., zero order absorption What happens after administration? drug may distribute into all of the accessible regions instantly because all of the accessible sites have the same distribution kinetics as if the drug is dissolved in a beaker containing a single solvent. Why it’s called like that? because unlike the beaker model the drug is eliminated from the container. What called ( Open ) ? One compartment open model Visuals: The time course of a drug which is handled in the body according to a one compartment open model depends upon the concentration which was initially introduced into the body (Co) and KE. Note that e-KE is the fraction already (t) eliminated: Formula: A plot of C versus t will be curvelinear on a linear paper and will be linear on a semi-log paper. What happens when IV bonus given? What is neglected? entire dose of drug enters body immediately. Rate of absorption In most cases drug distributes via the circulatory system to all the tissues in body and equilibrates rapidly in body. dx/dT = rate of process K e = elimination rate constant Rate of process involves firstorder kinetics X= amount of drug in body at any time t remaining to be eliminated Negative sign indicates that drug is lost from the body Elimination phase can be characterized by 3 parameters: Compartment Models 1. Elimination rate constant 2. Elimination half life tyke 3. Clearance Substituting plasma drug conc C in place of amount of drug in the body X One compartment open model ( IV administration ) Notes: Notes: When log c is plotted against time ton semilog paper we get a straight line with slope = overall elimination rate constant Elimination rate constant has units of min-1 Linear plot is easier to handle mathematically than a curve which is obtained by eqn 5. Plot of C versus time gives an exponential curve that is cartesian plot. For each drug the apparent Vd is constant. In certain pathologic cases apparent Vd for the drug may be altered if distribution of drug is changed. For example in edematous conditions total body water and total extra cellular water increase. This is reflected in a larger apparent Vd value for a drug that is highly water soluble. Similarly changes in total body weight and lean body mass which normally occurs with age may also affect the apparent Vd. Several advantages in giving a drug by intravenous infusion at zero-order rate: 1. In critically ill, antibiotics and drugs can often be conveniently administered by infusion together with IV fluids, electrolytes or nutrients. 2. The rate of infusion can be easily regulated to fit individual patient needs. 3. Constant infusion prevents a fluctuating peak (max.) and valley( min.) blood levels. Conc. of drug in plasma by IV infusion at avconstant rate is shown in fig. Plateau level is called the steady-state conc., Desirable if drug has narrow therapeutic index. After a while the drug accumulates to reach a plateau or steady state level. the point at which the rate of drug leaving the body and rate of drug entering the body (infusion) are the same. Q: increase in rate of infusion, time reach SS change? elimination half-life. This is reached in period of time equal to six times the elimination half-life. Time required to reach steadystate drug conc. in blood is primarily dependent on what? One compartment open model ( continuous IV infusion ) If drug is given at a higher infusion rate, a higher steady-state level is obtained, but the time needed to reach steady state remains the same as shown is fig. Notes: Notes: Amount of drug in the body is zero when constant rate of infusion is started and there is no elimination. As time passes, amount of drug in the body rises gradually until rate of infusion equals rate of elimination. i.e conc. of drug in plasma approaches a constant value called as steady state or plateau. At this stage e -ket becomes negligible. Equation: No, but amount reach is more