Pharmacokinetics Flashcards
Why is PK important?
ADME (absorption, distribution, metabolism, excretion)
Determines species specific drug behavior, arrives safe and effective doses, optimization of therapeutic concentration
Area under curve (AUC)
Expresses the total amount of drug that comes into the systemic circulation after administration
Why is AUC important?
Evaluates bioavailibility of a drug from its dosage form
Represent the extent of absorption
Bioequivalence
Comparing the generic version of a drug to a new one
C max and T max should be relatively equal
Volume of distribution
Vd= Dose (amount given) / Plasma concentration
When is there high Vd?
High tissue distribution
Low plasma tissue binding
More lipid soluble
Mainly in tissues
When is there low Vd?
Low tissue distribution
More water soluble
Mainly stays in plasma
High plasma concentration
High protein binding drugs
How do you determine dose?
Dose= Vd x target concentration
Vd of protein bound drugs
Limited to plasma
5% of body weight= 0.05 L/ kg
Vd of water soluble drugs
In extracellular fluid
20-30% of body weight=0.2-0.3 L/kg
Vd of lipid soluble drugs
Distributed in plasma
ECF and intracellular fluid (ICF) or total body water (TBW)
60-70% of body weight= 0.6-0.7 L/kg
Example for finding dose
Pentobarbital= highly LIPID SOLUBLE anesthetic agent
Vd= 0.6 L/ kg , target conc = 20 mg/L (given with drug)
Dose= 0.6 L/kg x 20 mg/L = 12 mg/kg
Elimination rate constant (k)
Fraction of the drug in the body removed per unit time
OR
Rate where plasma concentration declines during elimination phase
Zero order (drug elimination)
A fixed amount/ quality of drug processed per unit time
Ex: alcohol, phenytoin and salicylates
What does half-life of zero-order kinetics depend on?
On the dose administration (higher dose, higher half-life)
Examples of drugs in zero order
Salicylates in cats
Phenylbutazone in dogs and horses
half-life dose dependent
First order (drug elimination)
A fixed fraction or % of drug processed per unit time
Half life constant even with increased dose
Most drugs
For first order, when does complete elimination occur?
5 half-lives
Half-life
Time taken for the drug concentration to fall to half it’s original value
t1/2= 0.693 x Vd/CL
Short half-life
Indicates short duration (rapid elimination) and low concentration at the site of action
Why is half-life useful?
For determining an appropriate dosing interval
Determines time taken to achieve a steady state or equilibrium constant with any constant dose rate
Which drugs will have a long half-life?
Drugs widely distributed and sequestered in tissues
Which will increase half-life?
Enter-hepatic circulation and plasma protein binding
Renal and hepatic dysfunctions depending on route of elimination
Dosing interval
Time interval between doses that keeps plasma concentration of a drug within therapeutic range
How is dosing interval determined?
Max plasma concentration(Cmax) to drop below where desired response no longer occurs (MEC,Cmin)
What is recommended for therapeutic pruposes?
A dosing interval equal to or less than the elimination half-life
Steady state concentration
Time where concentration remains stable OR consistent when drug is given repeatedly or continuously.
Ex: IV infusion
When do you reach steady state?
When the rate of drug entering systemic circulation equals the rate of elimination
Approximately in 3-5 half-lives
One compartment
Whole body a single homogenous unit
Rapidly distributed drugs
Two compartments
Central comp- highly perfused organs
Peripheral comp- less perfused organs
Non-compartments
No assumption of any compartment
Derives pharmacokinetic parameters by simple algebraic equations
