PK 2 Flashcards
What is meant by quantitative pahrmokinetics?
Changes in plasma/ tissue drug concentration with time
What is the drug absorption rate?
The amount of drug absorbed from administration site to measurement site per unit time
What order of kinetics does oral/ IM routes take?
First order (zero order= IV infusion)
What are the kinetics from IV bolus administration?
Considered instant
Describe first order kinetics
- Absorption rate is proportional to amount of drug
Describe 0 order kinetics
-Absorption rate increases in a linear fashion with time. INDEPENDENT of amount of drug delivered.
What is the drug elimination rate?
Amount of PARENT drug eliminated from the body PER UNIT TIME
with respect to IRREVERSIBLE elimination of parent drug
What is Vi?
Initial volume - blood + interstitial fluid
Define Vd
Volume into which a drug appears to be distributed with a concentration equal to that of plasma
- Amount of drug in body at time (t)= Vd at time x blood/plasma conc at time
What affects Vd?
The affinity of the drug for plasma and tissue. Some prefer to move to tissues and so have a higher Vd
If Vd is 0.1-0.3L/kg what does it tell you about the drug?
That is is most likely water soluble and moves mainly to the ECF
If Vd is 0.6l/kg what does it tell you about the drug?
that most likely it distributes to BOTH ECF and ICF
If Vd is around 2l/kg what does it tell you about the drug?
that most likely is it accumulating at a particular site e.g. fat
What is total body (blood) clearance
The volume of blood/ plasma cleared of parent drug per unit time
(imagine it as flow rate)
How do you calculate elimination and clearance?
- Rate of elim= blood clearance x blood concentration
- Total clearance = Cl hep + Cl ren + Cl pulmonary
How do you determine total CL after IV bolus?
-Plasma clearance after IV bolus= Dose/ AUC
Describe bioavailability and calculating CL
Bio= the EXTENT (amount) of absorption from admin site to measurement site F= (Dose iv/ Dose oral) X (AUC oral/ AUC iv)
How do you calculate the elimination rate constant K?
=Clearance/ Vd
What is the elimination rate constant?
Constant relating to rate of elimination to the amount of drug in the body
How do you calculate the rate of elimination?
Plasma Cl x plasma concentration
Describe the one compartment model
- Assumed drug is instantly distributed
- Cl, Cd and half life are CONSTANT (exponential)
- therefore decay= Vd= Vi= Dose (C0)
What does the half life equal in a single compartment model?
natural log of 2 / elim K
0.0693 x Vd /Cl
In the 2 compartment model why is there 2 half lives and which is generally more important?
- Because of a change in Vd (implies Vs initially increases)
- Normally B but not always (the one with the biggest AUC)
How does Vd relate to kinetics of drug elimination?
- Phase 1: drug partitions into tissues
- Phase 2: drug slowly cleared from tissues
On average how many half lives does it take to reach steady state in multiple dosing?
around 5
How do you calculate average concentration ss?
Avrgconc ss = (Therapeutic dose x F)/ (CL x dosing interval)
Is Average concentration ss dependant upon Vd?
No it is independant
What is a loading dose?
An initial higher dose that it given to load up the tissues so you reach steady state quicker. You then drop down to maintenance dose.
Most useful for drugs that are eliminated slowly (have a long half life)
-Loading dose= (Therapeutic Css X Vss) / F
What is the importance of plasma half life and dosing frequency?
- Peak to trough is large when only giving 1 dose a day, means you run the risk of falling out the therapeutic window. Dosing more frequently can stop this.
Is plasma clearance always linear?
No
- it is driven by enzyme/ transported kinetics so saturation can occur.
- Vm x C/ Km x C
