General Aspects of Pharmacokinetics Flashcards
What is clearance? How is it expressed?
parameter describing drug elimination defined as the volume of plasma which contains the total amount of drug that is removed from the body
volume per unit time; mL/min, L/hr
What is clearance usually used to assess?
excretory capacity of an organ
What is renal clearance? How is it calculated?
volume of plasma containing the amount of drug that is removed from the body by the kidneys
What is the total body clearance?
sum of clearance rates for each mechanism involved in elimination of the drug
Clearance is the proportionality factor to….
determine the rate of drug elimination
Clearance does not describe….
the amount of drug being eliminated
What is the rate of drug elimination?
amount of drug being eliminated per unit time
How can overall clearance be estimated by measuring plasma concentrations at intervals following a single IV bolus dose (Q)?
AUC = area under the curve releating plasma concentration to time following a bolus dose
How can drug clearance be determined in an individual subject by measuring the plasma concentration of the drug at intervals during a constant-rate IV infusion?
X = Css x CLtotal
CLtotal = x/Css
What does a time curve during a constant IV infusion compare to following an IV bolus dose?
plasma concentration increases from zero to a steady state, and when the infusion is stopped, C declines to zero
plasma concentration rises abruptly and declines toward zero
What is the elimination half-life of a drug?
the time necessary for plasma or blood concentrations to decline by 50%; disappearance of drug from plasma
How many half-lives are necessary for a drug to be close to completely disappeared? What does it mean if a drug has a short half-life? Long?
by 5 half-lives, the drug will be 97% eliminated
the organ is rapidly clearing the drug
the drug persists within the body longer
How do changes in volume of distribution affect half-life?
increases in volume of distribution increases the half-life of the drug and extends the duration of action of the drug and vice versa
In what 3 clinical situations will the half-life of a drug increase? Decrease?
- decreased renal or hepatic blood flow due to hemorrhage, heart failure, or cardiogenic shock
- decreased renal function
- decreased metabolism caused by another drug inhibiting biotransformation or hepatic insufficiency
- increased hepatic blood flow
- decreased protein binding so that drugs can more easily pass through the glomerulus
- increased metabolism
What is first-order elimination?
the same volume of blood will be irreversibly cleared of drug by an organ regardless of how much drug is in the blood (independent of PDC) - every unit of time, half of the drug will be eliminated
the half-life of a drug will be constant regardless of drug concentration
Most drugs are eliminated using first-order elimination. When will drugs turn to zero-order elimination?
if the first-order elimination mechanisms become saturated due to a large concentration of drug present in the blood
(limited amount of enzymes and too much drug)
What is zero-order elimination?`
the rate of elimination of a drug from the plasma is constant regardless of plasma concentration, however, the half-life is not meaningful and a set amount of drug is eliminated per unit time
If a drug half-life is 2h, how long does it take the body to completely eliminate the drug?
a. 1 hr
b. 3 hr
c. 5 hr
d. 10 hr
e. 12 hr
E
2 hr = 50% of drug gone = 1 T1/2
5 T1/2 = most of drug gone
5 T1/2 = 10 hrs
10 + 2 = 12 hrs
Assume a dog has ingested several aspirin to the point that the PDC has surpassed the therapeutic range of 100-500 mg/mL and has achieved the toxic concentration of 2000 mg/mL. The half life of aspirin is 9 hours.
a. Assume it is eliminated by first-order elimination. What will the concentration be at by 36 hours?
b. Assume it is eliminated by zero-order elimination at 100 mg/mL of aspirin per unit time. What will the concentration be at by 36 hours?
a. FIRST-ORDER = half-life/time (50% aspirin/9 hrs)
2000 —> 1000 —> 500 —> 250 —> 125 mg/mL aspirin (safe!)
b. ZERO-ORDER = constant amount eliminated per unit time (100mg/mL /9hrs)
2000 —> 1900 —> 1800 —> 1700 —> 1600 mg/mL aspirin (still toxic!)
What common drug is eliminated using zero-order elimination?
the rate of elimination of ethanol from the plasma is constant, regardless of the dose or plasma concentration of the ethanol
True or false: In first-order kinetic elimination, the drug’s half-life decreases with time
FALSE - half-life remains constant
True or False: Drugs slowly eliminated require more frequent dosing.
FALSE
What 4 things does understanding pharmacokinetics help us do in clinical practice?
- interpret drug concentration
- adjust dose regimens rationally
- identify and evaluate possible drug interactions
- individualize dose regimen when dealing with a severely ill patient
In practice, pharmacokinetics focuses on what? What is therapeutic drug monitoring?
concentration of blood in the plasma, which allows for the individualization of dosages
achieving the desired therapeutic effect while minimizing adverse effects in each individual patient
What is pharmacokinetic modeling? What is its purpose?
when a drug of interest is given as a single dose and drug concentrations are collected over time, usually for at least 3 elimination half-lives to ensure that all phases of the drug movement are identified
predict the behavior of a drug in the body
How should a drug be administered for bioavailability studies using pharmacokinetic modeling?
intravenously as well as the route of interest
What is the one compartment (single) model for pharmacokinetic modeling? When is this model applicable? While it is useful, what should be considered?
the body is considered as a single homogenous compartment - the entire dose of a drug is assumed to move out of the body at a single rate
if plasma concentrations fall exponentially after drug administration
it is a physiological oversimplification, since the different parts of the body are quite different in terms of blood supply
What is the two-compartment model of pharmacokinetic modeling? Why is this usually used in pharmacology studied? What 2 things should still be considered?
model introduced another (peripheral) compartment to represent tissues in communication with the central plasma concentration
it resembles more closely to the real situation
- this model still uses an approximation by lumping all organs and tissues in the peripheral compartment
- this model assumes that drug molecules can only enter or leave the peripheral compartment through the central (plasma) compartment
When is the multicompartment model used? What is the third compartment considered?
experiments conducted over long time frames or in production animals
tissue residue of the drug in a food-producing animal’s product (meat, milk, etc.)
