Applied Pharmacokinetics

Question 1

(1) What is the key question around dosing regimens and how does that relate to concentration?

Answer 1

in determining the “How much, how often, how long?”; a relationship exist between the concentration of drug and pharmacological effect

Question 2

(1) How is the rate of change of drug in the body, defined by rate of absorption and rate of elimination?

Answer 2

rate of change of drug in body= rate of absorption- rate of elimination

Question 3

(1) Contrast zero-order and first-order elimination kinetics. (specifically their rate of change and drug concentration)

Answer 3

zero order: rate of change is independent of drug concentration (ie. when enzyme is saturated)

1st order: rate of change is directly proportional to drug concentration

Question 4

(2) What is the formula for volume of distribution?

Answer 4

Vd = A/C ….   A=VxC   … similar to D=m/V
A= amount of drug in body
C= plasma drug concentration 
Vd= volume of distribution

Question 5

(2) State conditions that may alter the volume of distribution.

Answer 5

urea and burn patients will have less blood albumin

in conditions of pregnancy and dehydration there is change in blood volume causing a change in the volume of distribution

renal end stage disease must be considered on a case by case basis for a given drug

Question 6

(3) State the first-order elimination formulae in terms of concentration or amount of drug.

Answer 6

dC/dt= -keC :: change in concentration over time is equal to the elimination rate constant (negative) times the concentration

Question 7

(4) Give the equation used for calculating plasma concentration or amount of drug in the body at a specified time after a single dose

Answer 7

C = C0 * e^-ket

Question 8

(5) State the elimination half-life formula.

Answer 8

t1/2= 0.7/ke; Ke= 0.7/ t1/2

Question 9

(5) After ___ half-lives, virtually all of the drug is eliminated.

Answer 9

After 5 half-lives, virtually all the drug is eliminated

Question 10

(6) Explain the meaning of clearance.

Answer 10

clearance is the product of the elimination rate constant and the apparent volume of distribution; is considered the fraction of fluid entering an organ from which all drug is removed

Question 11

(6) Relate clearance, elimination rate and volume of distribution.

Answer 11

Ke * Vd = CL

Question 12

(6) Define half-life using Vd and CL

Answer 12

t1/2 = (0.7*Vd)/ CL

Question 13

(5) Broadly, describe factors that affect drug half-life.

Answer 13

anything affecting Vd:
decreased total body water, 
increased tissue (obesity), 
increased nonvascular fluid
decreased albumin

anything affecting CL:
metabolism: CYP induction or inhibition
cardiac, hepatic or renal failure

Question 14

(6) Describe the “multiple interaction equilibria” that exist in drug metabolism.

Answer 14

drug can be bound or unbound in the blood and that equilibrium affects the equilibrium between the blood, tissues and drug elimination

Question 15

(7) Explain constant-rate infusion.

Answer 15

adding drug to the system in a way and at a rate that produces a stable plasma concentration – it produces a steady state

Question 16

(7) All drugs infused at the same rate and having the same clearance will reach the same ___ ___.

Answer 16

plateau concentration

Question 17

(7) With drugs of the same half-life, infused at the same rate, what is true about the amount in the body at the plateu

Answer 17

it is the same for all of drugs infused at same rate with the same half life

Question 18

(8) Calculate the rate of drug infusion given the elimination rate.

Answer 18

rate of infusion= rate of elimination = CL* Css

Question 19

(9) How are multiple-dose regimens related to constant rate infusion?

Answer 19

although multiple-doses are given in discrete fixed doses, the amount and steady state concentration will very; under fixed rate, fixed-interval dosing it takes 5 half-lives to achieve a plateau.

Question 20

(10) Give the equation for calculating the maintenance dose rate.

Answer 20

to maintain a plateau, rate of infusion= rate of elimination so when determining a maintenance dose, consider the elimination rate

Dm rate= CLCss or for intermittent doses Dm rate= CLCss* dosing interval

Question 21

(10) How do you insure that the Dm rate does not give concentrations outside the therapeutic window?

Answer 21

use the equations Dmmax= Vd/F (Cupper-Clower)

tmax= (ln (Cupper/Clower))/ke

Question 22

(11) Describe the equation used to calculate a loading dose.

Answer 22

A= Vd* desired plasma concentration

Question 23

(12) What affect does bioavailability have on drug dose?

Answer 23

only a portion of the dose taken not by IV reaches the blood stream, you must experimentally the percent of the dose that reaches the blood and correct for availability when dosing.

Question 24

(12) How do you calculate the bioavailability?

Answer 24

F= area under the curve-route/ area under the curve-IV

Question 25

(12) Contrast the plasma drug concentration for IV and oral routes of administration.

Answer 25

oral route causes a more subtle and extended increase in plasma drug concentration, oral route does not cause plasma drug concentration to increase as much as the IV route (which is a much stronger, sharper response in plasma drug concentration)

Question 26

(12) How do you correct for bioavailability?

Answer 26

divide the IV dose by the bioavailability (F) to get the alternate dosage