Flashcards in Lecture 5: Pharmacokinetics Part 3 Deck (18)
The elimination of most drugs under normal dose ranges is a
First order rate process
First order rate process
The rate at which a drug is excreted from the body is directly dependent on the amount of drug in the body.
Single Compartment Model
-Consider the body to be one unit which a drug distributes through instantaneously and evenly when injected via an IV bolus. With this model, we don't have to model absorption or distribution. We only model elimination of the drug over time.
The elimination rate constant; an inherent property of the drug.
Describe the first order rate process in relation to drugs
When the drug concentration in the body is high, the rate of elimination is high. As the drug concentration decreases, the rate of elimination also decreases.
Equation used to measure initial drug concentration
-Co: Initial drug concentration
-Vd: Volume of distribution
How do we calculate the concentration of a drug anywhere along a concentration x time graph?
By using the equation:
C= plasma concentration
Co= initial concentration
Vd= volume of distribution
The volume of plasma from which a drug is removed per unit time. It reflects elimination of drug through metabolism and various routes of excretion
Drug half life is (directly/inversely) proportional to its clearance
Inversely. The more quickly a drug is cleared from the body, the shorter its half life. As Cl increases, t1/2 decreases.
The half life of drugs with big volumes of distribution (Vd):
Is very long, because they are eliminated at very low rates.
When a drug is administered via continuous IV infusion, the plasma concentration quickly rises until it reaches a plateau where:
The rate of administration= rate of elimination.
Thereafter, the drug achieves steady state= Css
Multiple dosing to achieve steady state
If someone takes an orally administered drug, concentrations will quickly rise, hit a peak, and then the drug will start to be eliminated. If we give another dosage before the first one being completely eliminated, we can build upon the first dosage. We can keep doing that until we get oscillations between peaks (Cmax) and throughs (Cmin) in the plasma concentration which are around the mean steady state concentration. The [drug] stays within the therapeutic window.
With continuous IV infusion or repeated doses, Css is usually reached after:
3 half lives of the drug, regardless of what the drug is. This is a property of a drug that follows first order kinetics.
How do we achieve a therapeutic benefit upon first dosage with multiple dosing?
By giving a large initial dose (loading dose). This pushes the concentration up into the therapeutic window, and once it is there you can keep it there with smaller maintenance doses.
What happens if you extending the dosing interval? (the patient takes every second dosage or the amount of drug taken at each interval is decreased)
Reducing the rate of administration can lead to a lower than intended steady state plasma concentration (Css) and absence of a therapeutic benefit
Increasing the rate of administration could lead to:
The target concentrations strategy
-Based upon the fundamental linkage of pharmacokinetics and pharmacodynamics.
->Assumes that for most drugs the magnitude of therapeutic effect and risk for adverse effects in an individual is predictable for a given target concentration (TC) in the blood.
BUT, the dose required to achieve TC will vary between individuals