Pharmacokinetics Flashcards
Clearance
CL = rate of elimination/concentration
CL = Q(Ca-Cv)/Ca = QE
Body’s efficiency of drug removal;
Volume of fluid from which the drug is removed per time
Volume of Distribution
Vd = amount of drug in the body/concentration in blood
Apparent space drug resides in
Elimination Half Life
Rate of drug removal
Bioavailability
Fraction of Drug Absorbed
Dosing Rate
= dose/T
= CL * Css
goal is to maintain steady state concentration
Plasma volume
4L
ECF volume
12L
TBW
40L
elimination constant, Ke
= CL/Vd = 0.7/(t1/2)
One compartment open model
- single IV dose
- assumes entire body is one compartment
- assumes drug is distributed evenly
- assumes open system (excretion)
Two compartment model
- single IV dose
- assumes most of drug is in a particular compartment
- assumes equilibrium between blood and other areas
Multicompartment model
- needs computer assistance
- measures area under curve (AUC)
- more widely used than other models
- CL = dose/AUC
Predicted Css after various dosing schedules:
Css = (F * Dose)/(CL * T)
In a multiple IV bolus, time to steady state:
- is about 5 half lives
- independent of dose or dose interval but dependent on t1/2 (plateau principle)
IV infusion, Css =
infusion rate/total body clearance
Loading dose
- use it when you can’t wait for 5 half lives to achieve Css
- LD = (Css * Vd)/F
- but watch out for dangerously high volumes…
- maintenance dose: Dosing rate = (target Css * CL)/F
What does it mean for a drug to have zero order kinetics?
- Enzymes that metabolize the drug are saturated (are rate limiting) at normal drug levels in the body
- Same amount of drug metabolized regardless of drug level in the body
Zero order kinetics drugs
Ethanol Heparin Phenytoin Aspirin Amobarbital Tetracycline
For zero order kinetics, LD =
(Css * Vd)/F
For zero order kinetics, Css =
(Km * DR) / (Vm - DR)
Km = dose that produces 50% of maximal elimination rate Vm = maximal rate of process
For zero order kinetics, DR =
(Css * (Vm - DR)) / Km
Pharmacokinetics
Concerned with the disposition of the drug in the body
Ways to modify drug absorption
delayed release
rapid release
transdermal
depot preparations
Effect of stomach’s acidic environment on drug absorption
Acidic drugs will be nonionized and absorbed,
basic drugs will be ionized and won’t be absorbed until SI