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Week 3 - Biopharmaceutics and Pharmacokinetics

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## Week 3 - Biopharmaceutics and Pharmacokinetics

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**Week 3 - Biopharmaceutics and Pharmacokinetics**Pn. KhadijahHanimbt. Abdul Rahman School of Bioprocess Engineering University Malaysia Perlis**Drug Clearance**• Body is considered as a system of organs perfused by plasma and body fluids. • Drug elimination from the body is an ongoing process due to both metabolism (biotransformation) and drug excretion through the kidney and other routes.**Drug Clearance**• The mechanisms of drug elimination are complex, but collectively drug elimination from the body quantities using the concept of drug clearance. • Drug clearance refers to the volume of plasma fluid that is cleared of drug per unit time. • Clearance may also be considered as the fraction of drug removed per unit time multiplied by VD.**Drug Clearance**• The rate of drug elimination may be expressed in several ways, each of which essentially describes the same process, but with different levels of insight and application in pharmacokinetics.**Drug Clearance**• Drug Elimination Expressed as Amount per Time Unit mass approach: • For zero-order elimination process- expressing the rate of drug elimination as mass per unit time is convenient- rate is constant.**Drug Clearance**• Drug Elimination Expressed as Volume per Time Unit Clearance (volume) approach: • First-order elimination-drug clearance expressed as volume per unit time is convenient- it is constant**Clearance- the rate of drug removal in terms of vol. of drug**sol. removed per unit time. • Drug conc. in the body gradually decline by 1st order process- mass of drug removed over time, is not constant. • Rate of drug removal- dependent on the plasma drug conc. at all times. • Clearance- for 1st order process is constant. Clearance expressed in vol. per unit time rather than drug amount per unit time.**Clearance (volume) approach**Rate of drug elimination is Dividing both side by CP**Drug Clearance**• Drug Elimination Expressed as Fraction Eliminated per Time Unit Fractional approach**Fractional approach**• Consider a compartment volume, containing VD liters. • If Clis expressed in liters per minute (L/min), • then the fraction of drug cleared per minute in the body is equal to Cl/VD.**Clearance and Vol. of distribution ratio, CL/VD**• Fraction of Cl/VD-dependent on • VD • Rate of drug clearance from the body • If drug conc. = Cp, rate of drug elimination (in terms of rate of change in conc.) • 1st order process:**Equating the 2 expressions:**• 1st order rate constant= fractional constant Cl/VD**One-Compartment Model Equation in Terms of Cl and VD**• Substituting Cp0 and k Cp = Cp0e-kt**One-Compartment Model Equation**• The IV single dose Equation may be modified to calculate the elimination rate constant or half-life of a drug in a patient when two plasma samples and their time of collection are known:**One-Compartment Model Equation**• If the first plasma sample is taken at t1instead of at zero and C2is the concentration at time t2and t is set to (t2— t1).**One-Compartment Model Equation**• Rearrange: • Half-life:**Clearance from drug-eliminating tissues**• Clearance- applied to any organ involved in drug elimination. • 1st order elimination processes involved- clearance represents the sum of the clearances for each drug-eliminating organ:**Clearance from drug-eliminating tissues**• Drug clearance considers: - Drug in body evenly dissolved in a vol. of fluid (VD). • Plasma fluid conc. measured, clearance calculated as fixed vol. of plasma fluid cleared of drug per unit time. Unit for Cl = vol/time.**Clearance from drug-eliminating tissues**• Rearranging: • ClT is a constant, represents the slope of the line obtained by plotting dDE/dt versus Cp • 1st order elimination drug, rate of elimination dependent on the amount of drug remaining in the body**Clearance from drug-eliminating tissues**• Substituting the elimination rate: • ClT = product of VD and k- both are constant • As plasma drug conc. decreases during elimination, the rate of drug elimination dDE/dt will decrease but clearance remain constant.**Clearance from drug-eliminating tissues**• Clearance can also be determined directly from plasma drug conc. versus time curve: • Do = dose and**Elimination half-life (t1/2)**Definition:Elimination half-life is the time it takes the drug concentration in the blood to decline to one half of its initial value. The elimination half-life is dependent on the ratioof VD and CL. Unit : time (min, h, day)