Intro to Pharmacokinetics and Application

Question 1

IV infusion

Answer 1

administration of drug is at constant rate
zero order process
elimination is a first order process

Question 2

Steady state (Css)

Answer 2

rate in (infusion) = rate out (elimination)

Question 3

Maintenance dose

Answer 3

amount removed

Question 4

Infusion rate

Answer 4

clearance x Css

Question 5

Clearance

Answer 5

volume of plasma cleared of drug in unit time

L/h

Question 6

Half life

Answer 6

time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%

Question 7

Volume of distribution

Answer 7

apparent volume in whcih a drug is dissolved in the body

amount in body / concentration = dose / conc at t=0

Question 8

Area under curve

Answer 8

conc against time

Question 9

First pass effect

Answer 9

phenomenon of drug metabolism where concentration of drug (normally po) is reduced before systemic circulation
absorbed into liver and gut wall

Question 10

What is the shape of plasma level/time curve of oral dosing influenced by?

Answer 10

rate of dissolution

rate of absorption

Question 11

Types of formulation for oral dosing?

Answer 11

rapid-release: quick peak, absorption and elimination

sustained-release: prolonged absorption super-imposed on elimination, not true half-life

Question 12

Bioavailability

Answer 12

the fraction absorbed (F)

F = AUC oral / AUC iv (100%)

Question 13

Dose given calculated with bioavailability and amount needed

Answer 13

amount needed / F

Question 14

What affects the time taken to reach steady rate when repeated oral dosing is given?

Answer 14

varied half lives of the drugs

independent to dosage

Question 15

What causes fluctuations when repeated oral dosing is given?

Answer 15

proportional to dosing interval/half-life

blunted by slow absorption

Question 16

What affects the steady state concentrations when repeated oral dosing is given?

Answer 16

proportional to dose/dosing interval

proportional to F / CL

Question 17

For oral regimen, how to calculate dose?

Answer 17

CL x Css x tau / F

where tau = dosage interval

Question 18

Important measures when designing a regimen

Answer 18

1. therapeutic window
2. urgency of onset of effect
3. elimination, half-life

Question 19

Importance of therapeutic window when designing a regimen

Answer 19

large TW (penicillins) - maximal dose strat
small TW - target level strat

Question 20

Importance of urgency of onset of effect when designing a regimen

Answer 20

may have to give a loading dose, followed by maintenance dose to keep up with elimination

Question 21

Loading dose

Answer 21

target level x V/F

Question 22

Maintenance dose

Answer 22

target level x CL/F

Question 23

importance of elimination and half-life when designing a regimen

Answer 23

short < 1 hour - large TW, large dose at convenient intervals
- small TW, infusion +/- loading dose
moderate 4-24hrs - initial dose, then half hthat every half-life
long >24hrs - set 24hr dosage interval to ensure best p compliance

Question 24

Complications with Gentamicin

Answer 24

toxic to ears and kidneys when dosage too high or low
even when low, still in bacteria taking effect (post-antibiotic effect)
largely renally cleared -> Cl = Cl creatinine