Test 1 Pharmacokinetics Flashcards
What is the basic principle of pharmacokinetics?
- The effect of a drug is related to the blood concentration of the drug.
- Therefore, changes in blood concentration will modify the effect of the drug.
Define and describe Bioavailability
- Fraction of unchanged drug reaching the systemic circulation after administration.
- Drugs administered by intravenous route have a bioavailability of 1, all other routes are < 1.
- Bioavailabilty is denoted in most formulas by “F”.
How is bioavailabilty determined?
- Comparing plasma concentration of drug over time between IV route and other routes.
- The area under the curve (AUC) vs. time is an index of the extent of drug that enters the bloodstream and thus the body.
What is the bioavailability equation?
F = AUCoral
AUCiv
Define and describe Half-life?
- Half-life is the time needed for a 50% decrease in plasma drug concentration
- Denoted as t1/2
- Expressed in units of time (usually hr)
What is the Half-Life formula in a one compartment model when the elimination rate constant (ke) is known.
t1/2 = (Ln 2)/ke = (0.693)/ke
What is the four half lives rule?
- A drug is considered essentially eliminated from the body after 4 half-lives.
- 94% of the drug is eliminated and only 6% remains in the body.
Define and describe Volume of distribution
- The apparent volume that a drug would be distributed within the body once an equilibrium is established with palsma.
- Denoted by Vd
- Expressed in Liters or Liters/kg
- Volume of distribution is an apparent volume.
Large volumes of distribution are an indication of a drug that is?
Highly lipophilic or has low protein binding.
What is the formula for Vd?
Vd = Dose(iv)
C0
How can Vd be graphically determined?
Using Plasma concentration at time 0.
Define and describe Clearance?
- Clearance is the volume of plasma from which a drug is totally removed per unit of time.
- Usually expressed as L/hr or mL/min
- Drug can be removed by metabolism or excretion
Total Body clearance definition
Sum of all clearance values for a drug and are additive.
CL total = CLrenal + CLhepatic + CLother
What is the formula for clearance?
CL = Ke x Vd
Formula for clearance, when Ke = 0.693/t1/2
CL = 0.693/t1/2 x Vd
Rearranged for halflife:
t1/2 = (0.693 x Vd) / CL
The half life of a drug is dependent on what?
Clearance and Vd
If clearance decreases and Vd stays the same what happens to half-life?
Half-life increases.
Assuming a single drug administration, plasma concentration is ______ _________ to the dose administered. Provide the formula for this aswell.
- Directly proportional
- A = C x Vd
- A = amt of drug
- C = plasma concentration
- Vd = volume of distribution
Define and describe First Order Elimination Kinetics?
- Definition: The rate of decrease in drug concentration is directly proportional to the amount of drug in the body.
- A constant fraction of the drug is eliminated.
- Elimination rate (Ke) is a constant.
Most drugs follow what order kinetics?
First order Kinetics
In First Order Kinetics the elimination rate (Ke) is a constant.
What does this mean?
-
Fraction of drug removed at any given time is constant and independent of dose.
- Constant fraction eliminated.
What does a graphic examination of first order kinetics look like.
The semi-log plot for one compartment first order kinetics will be a straight linear line.
Define and describe One Compartment model including what its graphical model looks like.
- A drug rapidly equilibrates between plasma and tissue relative to its elimination rate. The body acts as a single compartment.
- Semi-log plot of plasma concentration over time is a straight line when the drug follows first order kinetics.
-
Changes in plasma concentration reflect a proportional change in tissue concentration.
- The plasma and tissue concentrations may be different.
- The drug does not inherently distribute to all tissues.
Define and describe the Two compartment model:
- A drug takes a longer time period to establish equilibrium between plasma and tissue
- Drug has two compartments for distribution:
- Central and a peripheral compartment.
- Drugs can move between these two freely.
- Elimination occurs from the central compartment.
- Central and a peripheral compartment.
- Drug has two compartments for distribution:
Graphically describe the semi-log for two compartment model
- The semi-log plot results in two phases when the drug follows first order kinetics.
- Initial distribution phase (more rapid decline in plasma drug concentration over time
- Elimination phase (less severe continous decrease.
Describe Zero Order Kinetics
- Definition: A constant amount of a drug is eliminated independent of dose; the enzymes involved in elimination are saturated.
Define and describe Concentration at steady state (CSS)
-
The plasma plasma concentration maintained at Steady state
- Attained after 4 half-lives.
- CSS: rate of administration = rate of elimination
Define and describe Maintenance Dose:
- Dose taken at regular intervals to keep concentration within a trough and peak.
- The fluctuations between the peak and trough are dependent on the dosing interval.
- The longer the dosing interval the greater the variation in peak and trough values.
Mathematical formula for CSS?
- *CSS = MD**
- *CL**
Mathematical formula for maintanence dose
**MD = _Dose x F_ Dosing interval(t)**
t = dosing interval (its actually a greek t)
Equation for CSS for constant IV infusion
- *CSS = Infusion rate**
- *CL**
Define and describe a loading dose?
Equation?
A single large dose that can be given to produce an immediate rise in plasma drug concentration.
Loading Dose = CSS x Vd
F
What is the Ke for a drug with a half-life of 3 hours?
Ke = 0.693 = 0.231 h-1
3h
