Pharmacokinetics I and II Flashcards
Clinical Pharmacokinetics
Is concerned with the following quantitative (measured) parameters:
- Clearance - body’s efficiency of drug removal
- Volume of distribution - apparent space the drug resides in
- Elimination half-life - rate of drug removal
- Bioavailability- fraction of drug absorbed
Why is it necessary to understand clinical pharmacokinetics?
- There is a relationship between concentration of drug (from an accessible compartment) and its effects
- Develop a rational framework for dosing
- Improve therapeutic efficacy by selecting dosing regimens to match patients parameters
What is the most important concept to be considered when a rational regimen for long-term drug administration is to be designed?
Clearance (CL)
Define clearance
theoretical volume of fluid (i.e. blood, plasma) from which a drug is removed per unit time.
The clinician usually wants to maintain steady-state concentrations of a drug within the therapeutic window. How must it be administered?
Thus one needs to administer the drug at the same rate it is eliminated
Dosing rate = CL x CSS
What is the dosing rate equation?
Dosing rate = CL x CSS where CL is clearance from the systemic circulation and Css is the
steady-state concentration of the drug.
What is the equation for clearance?
CL = rate of elimination/ concentration
Systemic clearance is the sum total of clearance by the various organs: give the equation
CL = CLrenal + CLhepatic + CLother
What is the rate of elimation equation for an organ?
The rate of elimination of an organ = Q x CA – Q x CV = Q x (CA – CV) where Q is the blood flow to the organ.
The clearance for the organ is then defined as:
CL = Q[(CA – CV)/ CA] = Q x E where E is referred to as the extraction ratio.
What is the limiting variable no matter the organ wrt clearance?
it is important to note that blood flow (i.e. presentation of the drug) to the organ is the limiting variable.
Wrt elimination, there are 2 types of kinetics. describe them
Two distinct types of kinetics:
First order kinetics (most drugs obey first order kinetics)
Zero order kinetics (also known as saturation kinetics). Only a few, but some very important drugs obey zero order kinetics.
What does the graph look like for the kinetcs of elimination?

The slope of this straight line is what for a particular drug? and what does it mean?

the elimination rate constant (Ke) for that particular drug.
This means that a constant fraction of drug is eliminated per unit time.
The absolute amount of drug removed from per unit time will be concentration-dependent
What is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%?
Half-life: (t1/2)
What is volume of distribution?
give the equation
- Vd = Amount of drug in the body / C (Blood concentration )
- The fluid volume that would be required to contain all of the dose at the same concentration as exists in the blood or plasma.
For some drugs the Vd describes what? for other the Vd does what?
the primary fluid compartments in which a drug is distributed.
Give the quantities of the fluid compartments wrt plasma volume, extracellular fluid volume, total body water
plasma volume is 4 liters
Extracellular fluid volume is 12 liters
total body water is 40 liters
Describe the Elimination half-life (t 1/2 ) wrt the elimination constant. give equations and work a sample out when C/Co = 2
CL / Vd = (ml/min) / ml = 1/min = elimination constant (Ke)
The change is [drug]p with respect to time is therefore: dC/dt = -Ke ln (C/Co) = -Ke * t or ln (Co/C) = Ke * t
ex:When Co/C = 2: ln 2 = Ke * t 1⁄2
because ln 2 = 0.693 Ke = 0.693 / t 1⁄2 Ke 0.7/ t 1
What are the 4 Clinical importances of half-life determination?
- Determine dosing interval. A drug is usually given at half-life intervals.
- A factor in determining dose. .
- May determine route. Drugs with very short half-lives are preferably given I.V. or by sustained release tablets.
- Provides a good indication of the time required to reach steady-state after a dosage regimen is initiated.
Of the Pharmacokinetic Models, describe the “one compartment open model (single IV dose)”
For many drugs this is an adequate representation.
- Assumes entire human body is one compartment.
- This works for drugs that are distributed fairly uniformly throughout the body.
- Assumes an open system (excretion). Is not adequate for all situations.

Of the Pharmacokinetic Models, describe the Two compartment open model. Draw a graph to represent it showing the elimination and distribution phases
Assumes that much of a drug is in a particular compartment and that an equilibrium exists between the blood and other areas. (single IV dose)

Of the pharmacokinetic models, describe the Multicompartment models. Draw graph and give equation clearance wrt AUC when using the mulicompartment model
Requires computer assistance
Measures area under the curve (AUC)
More widely used that first two models.
With a multicompartment model:
CL = dose / AUC

What are the results from first pass metabolism or poor absorption parameters?
bioavailability is decreased
only a fraction of drug dose may have access to the systemic circulation. This is often the case with oral administration.




