Clinical Pharmacokinetics 1 Flashcards
Pharmacokinetics parameters
Volume of distribution
Clearance
Bioavailability
Volume of distribution Vd =
Amount of drug in the body/plasma drug concentration
Unit: volume
Vd is the volume required to
Contain all of the drug in the body at the same concentration as it is in the blood
Vd =
With respect to C0
Dose/C0
Plot of plasma drug concentration vs. time of IV bolus
Rapid fall: distribution phase
Slower phase: elimination phase
C0 is the intercept of y-axis and linearized elimination phase
To achieve quickly a target plasma drug concentration
Dose =
Vd * TC
Clearance (CL) is defined as
The volume of blood cleared of drug per unit time
CL =
Rate of elimination of drug/plasma drug concentration
Unit: volume/time
First order elimination
Rate of elimination = CL * C
CL is constant
Rate of elimination =
Vmax * C/(Km+C)
First order kinetics
Rate of elimination =
Vmax * C/Km
CL = Vmax/Km
Log of C vs. t gives a
Straight line
Half-life is a _________ for drugs eliminated by first-order kinetics
Constant
Steady-state concentration
Css
The plasma concentration when the amount administrated per unit time is equal to the amount eliminated per unit time
Steady state is attained after ____ half-lives
4
Equation for half-life
t1/2= 0.693*Vd/CL
Doubling the infusion rate
Doubles the Css
But same 4 half-lives to reach Css
Saturation kinetics of elimination when C exceeds Km
Rate of elimination = Vmax * C/C=Vmax
Examples of zero order = saturation kinetics
Aspirin at high doses
Ethanol
Phenytoin
Properties of saturation kinetics
Rate of elimination is maximal and independent of drug concentration
Zero-order elimination
A constant amount of drug is eliminated per unit time
Plot of C vs. t is linear
Drug is removed at a constant rate
CL is not constant. CL = Vmax/(Km+C)
Hal-life is not constant. No longer 4 half-life
Properties of first order kinetics
The concentration at a later time will depend on the rate of elimination of the drug
The drug concentration decays exponentially
Rate of elimination is directly proportional to drug concentration
A constant fraction of the drug is eliminated per unit of time
