ــــــــــــــ February 17 th, PHT - PRACTICAL Pharmacokinetic Basic Calculations Dr. Ahmed Alalaiwe

After this lecture, you will be able to: Calculate the rate of elimination (Ke) Get familiar with different methods of calculating AUC Memorize the units of different PK parameters Objectives

Elimination Rate Constant (Ke) overall elimination rate constant describing removal of the drug by all elimination processes including excretion and metabolism Ke

Proportionality constant relating the rate of change drug concentration and concentration It describes as : Ke = - dCp/dt Cp Ke

Equation: Unit of Ke: Ke

Examples: DrugKe (1/hour) (hour -1 ) Acetaminophen0.28 Diazepam0.021 Digoxin0.017 Gentamicin0.35 Lidocaine0.43 Theophylline0.063 Ke

Cp, Ke and time relationship Ke

Area Under the Plasma Curve (AUC) AUC

Can be calculated by: Trapezoid method Segments method AUC

AUC 2-3 = Cp 2 + Cp 3. ( t 3 – t 2 ) 2 Trapezoid Method

The first segment can be calculated after determining the zero plasma concentration Cp 0 by extrapolation AUC 0-1 = Cp 0 + Cp 1. t 1 2 Trapezoid Method

final segment can be calculated from t last to infinity: Trapezoid Method

TimeConc 0Unknown Exercise

Calculate Ke: ln(x)= log(x) Time ln (Conc) 0Unknown TimeConc 0Unknown Exercise

Slope = = /time Extrapolation of Cp 0 Cp = 71 Ke = Cp0 = 100 Exercise

Calculation of first segment: AUC 0-1 = Cp 0 + Cp 1. t1 2 = ( )/2. 1 = 85.5 Calculation of last segment: AUC 0-∞ = Cplast / K = 3.1 /0.34 = 9.11 timeconcAUC = Cp last 9.3 ??? Exercise

Total AUC: timeconcAUC = AUC last total292.1 Exercise

mass. time / volume mg.hr/L Units

A graph of log A versus t will yield a straight line The y intercept will be log A 0 The slope of the line will be –k/2.3 Similarly, a graph of log C versus t will yield a straight line. The y intercept will be log C 0, and the slope of the line will be –k/2.3 First Order

Homework