Clinical Pharmacokinetics

Question 1

Clinical pharmacokinetics

Answer 1

the mathematical description of the time course of disposition (ADME) of drugs in the body

Question 2

Basic hypothesis of clinical pharmacokinetics

Answer 2

A relationship between the pharmacological effect of a drug and the concentration of that drug in the systemic circulation

Question 3

Key concepts of pharmacokinetics

Answer 3

1. bioavailability (F)
2. Volume of distribution (VD)
3. Clearance (CL)

Question 4

One compartment model

Answer 4

-simplest model, assumes that body acts as a homogenous single compartment (“in and out”)

-true for many drugs that distribute rapidly (ex. highly lipophilic)

Question 5

Keys to compartment model graphs

Answer 5

-Will have log blood plasma concentration (Cp) on y axis, and Time on x axis

-One compartment= linear line

-Two compartment= kink in model (first part displays distribution, second part displays elimination)

Question 6

Two compartment model

Answer 6

• involves absorption into central compartment, and then diffusion into peripheral compartments

-rates will change based on equilibrium of free drug

Question 7

Physiologically-based pharmacokinetic (PBPK) models

Answer 7

-most realistic because looks at all the different compartments of the body and their individual concentration and blood flow

Question 8

When are PBPK models used?

Answer 8

-only used for drugs that don’t behave “normally”/ have a narrow therapeutic window

-usually dangerous drugs where the research and costs will be worth it!

Question 9

Key to first or zero order graphs

Answer 9

**will have plasma drug concentration on y axis, and time on the x axis

First order= curved line
Zero order= straight line

Question 10

First order pharmacokinetics

Answer 10

Elimination is proportional to the plasma drug concentration

-used for most drugs
-high concentrations eliminated fast, low concentrations removed slowly

Question 11

Zero order pharmacokinetics

Answer 11

Elimination is independent of plasma drug concentration (“Constant elimination”)

can be dangerous when drug concentrations are high and cannot be eliminated any faster

Question 12

Ethanol as a zero order kinetic drug

Answer 12

-can only metabolize a certain amount at a time

-constant elimination so when more ingested, cannot rid it from the body any faster

Question 13

Steady state (repeat dosing)

Answer 13

-attained after approx 4 half times
-time to a steady state is independent of dosage

Question 14

Steady state concentrations

Answer 14

-proportional to dose/dosage interval
-proportional to bioavailability/clearance

Question 15

Steady state fluctuations

Answer 15

-proportional to dosage interval/half time
-blunted by slow absorption

Question 16

Dose interval influence on steady state

Answer 16

The perfect dosage is between max safe concentration and minimum effective concentration
>if too minimum then not effective, and if too much then unsafe/toxic

Question 17

Enzyme saturations impact on order kinetics

Answer 17

a drug can exhibit first order kinetics at lower doses and then switch to zero order kinetics at higher doses due mainly to saturation of biotransformation enzymes