Module 3: Principles Of Pharmacokinetics Flashcards
What does LADME stand for?
L = Liberation (release of drug from formulation)
A=Absorption (uptake of drug into circulation
D= Distribution (movement of drug around body)
M= Metabolism (effect of enzymes on drug)
E=Excretion (removal of unchanged drug or metabolite from body)
How can system exposure of a drug be evaluated?
With an index of systemic availability of the drug.
Measurements from circulation or body products (plasma, serum, blood, urine, saliva etc)
What are some disadvantages of using plasma drug concentrations?
The measurement includes bound and unbound drug (bound is the drug that is bound to plasma proteins forming a reservoir).
Bound is not actually available to exert an effect.
Assumes circulation is good enough to get the drug to tissues (ie can be impacted by atherosclerosis)
Assumes homogenous distribution of drug, which may not be possible (ie not in equilibrium between blood and rest of body)
What is Cmax?
In an Exposure-Time graph, the maximum concentration (peak of the graph)
What is tmax?
In Exposure-Time graph, the time at which Cmax is reached
What is t1/2?
The half-life of elimination of the drug (the amount of time to reduce the amount by half)
What is CL?
Clearance - the quantity of blood that has drug removed from it over time (ie ml/min) - but doesn’t include the bound
What is Vd?
A Theoretical volume that represents the degree to which drug is distributed around the body (in L/kg ie 0.14L/kg)
Vd=V
Small V =restriction to blood or small subset of tissues
Large V =association with multiple proteins per cell
In an Exposure-Time graph, what is the significant of area under the curve (AUC)?
AUC is an index of total systemic exposure to drug (amount over time)
What are the 2 methods for finding AUC?
Trapezoid rule (draw straight line between 2 points and calculate as a trapezoid)
Simpson’s rule (fit a parabola to the line between 2 points and calculate from that)
What is the equation for trapezoid rule?
AUC = ((y2+y1)/2) * (x2-x1)
(For one trapezoid)
Then add them up
What is First Pass Metabolism?
Aka first pass loss - when oral drugs have loss of dose in GI tract from hepatic portal system and passing through liver before hitting systemic circulation. Also can be lost by gut bacteria etc.
What is bioavailability?
The proportion (% or fraction) of drug that is available to circulation.
100% if IV, may be less than 100% for other routes of administration
It reflects the dose and rate of administration
What is disposition?
It is comprised of distribution and elimination
What is the enterohepatic cycle?
Where the drug associates with the bile, end up back in the intestine, goes back through hepatic portal system to the liver and back into bile, cycling through.
Forms a reservoir.
