Clinical Pharmacokinetics Flashcards
clinical pharmacokinetics applies
pharmacokinetic concepts and principles in order to design dosage regimens qhich optimize the therapeutic reponse of a drug while minimizing the chance of adverse reactions.
plasma concentration of a drug is a function of
rate of input into plasma, rate or distribution to the tissues and rate of elimination
Volume of distribution
measure of apparent space in the body available to contain the drug
Vd= amount of drug in the body/ plasma drug concentration.
Vd= Dose/ concentration at time 0
If you want to acheive quickly a target plasma drug concentration (TC) we can calculate the dose required with
Dose=Vd x TC
High Vd will have high concentrations in extravascular tissue
Low Vd will have high concentrations in the blood plasma.
Clearance
measure of the body’s ability to eliminate drug
volume of blood cleared of drug per unit time and predicts the rate of elimination of the drug in the drug concentration.
CL= Rate of elimination(amount/time) / Plasma drug concentration (amount/ volume.
when 1st order clearance = dose/ AUC (concentration of drug in the systemic circulation as a function of time.
CL= Vmax/ Km+C- zero order kinetics.
when C «Km it becomes first order and reverts back to Rate of elimination = CLxC
Bioavailability
the fraction of drug absorved as such into the systemic circulation
Total body clearance
sum of all the different clearance processes for a given drug (kidney and liver major sites
Rate of elimination
CL x C= Rate of elimination
CL is a constant a ratio of rate elimination to plasma concentration is the same regardless of plasma concentration.
when a drug is 1st order, a constant fraction of the drug is eliminated per unit time and rate of elimination is directly proportional to drug concentration.(drug concentration decays exponentially plotting the log of a drug concentration against time yields straight line.
When 0 order and elimination is saturated. constant amount of drug is eliminated per unit time and clearance will vary.
RoE= Vmax x concentration/ Km + cencentration. Km= plasma concentration at which half of the maximal rate of elimination is reched. Vmax = maximal rate of elimination
Half Life.
.0693 x Vd / CL = t 1/2
indicates the time required to atain a 50% steady state level during constant infusion or decay 50% from steady state level during elimination.
determines the rate which blood concentrations rises during a constant infusion and falls after administration is stopped.
during constant rate of infusion, 50% is reached after 1 half life, 155 after 2, 87.5 after 3 and 94% after 4
during elimination, it is the same percentage but that is how much you lose
Factors affecting half life
obesity and pathologic fluid have an effect on Vd and increases half life by increasing Vd
the following lower clearance which increases half life- Aging, CYP inhibition, cardiac failure, liver failure, renal failure
CYP induction increases clearance which decreases half life.
Maintenance dose
used to maintain the plasma concentration within a specified range over long periods of therapy,
MD= Dosing rate x dosing interval.
Loading dose
used if it is necessary to acheive a target plasma level rapidly.
used to load the Vd with the drug.
(when dosing is condtant).Loading dose = desired peak Concentration x Vd / F(Bioavailability) x S(salt fraction)
To match the steady state peak concentration the loading ose = MD x Acummulation factor
dosing pland
based on knowledge of botht minimum toxic concentrations for a given drug as well as its clearance Vd and bioavailability
Dosing rate at steady state=
rate of elimination at steady state = CL x Target concentration / F
IV infusion-
the plasma concentration of drug ries from zero at the start of infusion until the rate of drug eliminated form the body balances input rate. when SS is achieved when rate of drug elimination is equal to rate of administartion.
Rate of elimination =Infusion rate- CLx Css
Concentration at steady state
Css= Infusion rate/ CL
