PHARM: Clinical Pharmacokinetics Flashcards
True or False: IV administration is the fastest route of drug absorption.
False- when administered via IV, there is no drug absorption
How can the rate of elimination of a drug be calculated in a one-compartment model?
Rate of Elimination (Vel)= Inherent rate of Elimination (Kel) * [Drug] in the body ([A]c)
What does it mean if a drug follows a 1st order process of elimination?
The drug elimination is proportional to the drug concentration in the body
True or False: Kel is a constant for a particular drug.
False: Kel can be different from individual to individual and can be different in the same individual at different times
How can Kel be determined from a Semi-log plot of [drug] vs. time?
Kel is the slope of the line
What is the half life of a drug?
The time it takes for half of the drug to be eliminated from the body
What is the relationship between half-life and the elimination rate constant for first order drugs?
Kel=0.693/T(1/2)
What sorts of drugs are zero order drugs?
Drugs whose metabolism or elimination is mediated by proteins, and thus, is saturable
What is the appearance of a regular and semi-log plot of a zero order drug?
Regular plots show a linear decrease, and semi-log plots are concave downward until the rxn is no longer is zero order
How can the rate at which a drug is absorbed be calculated for a drug administered extravascularly in a one compartment model?
Rate of absorption (Vabs)= absorptive rate constant for the drug (Kabs) * concentration of the drug at the absorptive site ([A]a)
How can a drug following a one-compartment model and in a first order process be identified by looking at a semi-log plot?
The semi-log plots for these drugs will simply be a straight line
Following administration into a two compartment model via intravascular bolus and accumulation in the central compartment what two process can happen to the drug?
Elimination or Distribution to peripheral compartment
How can distribution from the central to peripheral compartment be calculated?
Vcp= Kcp (rate constant for drug describing ability to distribute from central to peripheral compartments) * [A]c (conc. of drug in central compartment)
How can distribution from the peripheral to central compartment be calculated?
Vpc= Kpc * [A]p
On a regular plot of a two compartment model drug what is alpha and what is beta? What is happening to the drug during those periods?
Alpha is the distribution phase that consists of the rapid decrease in [drug] from initial concentration. Beta is the disposition phase, which consists of distribution, redistribution, and elimination of drug
How can beta be calculated for a two-compartment model drug?
Beta= 0.693/T(1/2)beta, where T(1/2)beta can be determined by using the linear portion of a semi log plot (indicating the cessation of distribution/redistribution)
What are the three phases of a semi-log plot of a drug administered extravascularly into a 2 compartment system?
Absorption, Distribution, Disposition
What is the utility of apparent volumes of distribution?
Gives an idea on where a drug goes once it enters the body
How can apparent volumes of distribution be calculated?
Give a patient a drug of a known amount, take blood levels (concentration) over time and then extrapolate the concentration to time point 0 prior to any elimination. Dividing the amount of drug by the concentration at time 0 will give the apparent volume of distribution
A drug is given to a patient and has a calculated apparent volume of distribution equal to 5.5 L. Where is the drug primarily located?
Within the vasculature
A drug is given to a patient and has a calculated apparent volume of distribution equal to 14.6 L. Where is the drug primarily located?
In the vasculature and ECF
A drug is given to a patient and has a calculated apparent volume of distribution equal to 105.5 L. Where is the drug primarily located?
Some tissue compartment of the body
What is bioavailability?
The fraction of drug that reaches systemic circulation- essentially a measure of absorption of a drug and how effectively it is absorbed
How can bioavailability be determined?
First administer a drug via IV, measure drug concentration over time and measure the area under the curve of a regular plot. Next administer the drug via extravascular route and obtain the area under the curve. Bioavailability (F)= AUCx/AUCiv
What is the interpretation of “When administered sublingually, THC has an F of 1?”
All of the THC that would have entered into systemic circulation directly via IV is the same amount that would get into circulation via sublingual administration
What is clearance?
The theoretical volume of fluid from which a drug is completely removed in a given period of time
What two equations can be used to determine total clearance?
Clt=Kel * Vd; =Xo/AUC
What is the extraction ratio and how is it calculated?
E is the efficiency at which an organ extracts a drug and is =(Cin - Cout)/(Cin)
How could one determine clearance of a drug from the liver?
Clh= Q (rate of blood flow) * E
What are the three processes that contribute to renal clearance of a drug?
Glomerular filtration, Active secretion, passive reabsorption
How is renal clearance of a drug calculated?
Clr=Clglomfilt + Cl (actsec) - Cl(tubReab)
What is the minimum effective concentration?
The concentration of a drug needed to produce its pharmacological effect
What is the steady state concentration?
The concentration at which a drug administered continuously has a dose rate = rate of elimination such that the blood concentration of a drug remains stable
How can steady state concentration be calculated
Css=dose rate/ Ct or dose rate/ Kel * Vd
When administering a drug via IV infusion how long does it take for a drug to reach half of its steady state concentration?
One half life
When administering a drug via IV infusion how long does it take for a drug to reach its steady state concentration?
4-5 Half lives
How does increasing the frequency of a smaller dose of a drug effect its pharmacokinetics?
There is smaller fluctuations in the concentration level
What is a loading dose? When is it needed? How can it be calculated?
A loading dose is a higher first dose given when the therapeutic window must be reached quickly. Loading dose (X*)=Css *Vd
How would a graph of multiple IV administrations differ from a graph of multiple extravascular administrations?
The spikes on the fluctuations would be more rounded due to absorption slowing down the process
How can the steady state concentration of a drug administered multiple times be calculated?
Css= (F*dose rate)/Clt
