Pharmacokinetics II

Question 1

elimination half-life

Answer 1

time necessary for the amount of drug in the body to decrease by 50%

during the elimination phase, this is the time for plasma concentrations to decrease by 50%

Question 2

drug elimination equation expressed in terms of concentration C

Answer 2

C = C(0)e^-kt

Question 3

What is the equation for elimination half-life?

Answer 3

t(1/2) = 0.693/k

Question 4

What is the mathematical relationship between clearance and dose?

Answer 4

CL(E) = Dose/AUC

Question 5

calculating volume of distribution from elimination clearance and slope

Answer 5

V(d) = Cl(E)/k

Question 6

relationship between Cl(E) and V(d) with elimination half-life

Answer 6

t(1/2) = 0.693V(d)/Cl(E)

individual variability in t(1/2) reflects variability in V(d) and Cl(E)

Question 7

plateau or steady state principle

Answer 7

during an infusion, the rate of change in the amount of drug in the body is the difference between the infusion rate and the rate of elimination

at steady-state that rate is zero, and C(SS) = I/Cl(E)

the drug concentration during an infusion can be considered to be a fraction of the eventual steady-state concentration (FC(SS)) which is the difference between C(SS) and the exponential decline from C(SS) so:

FC(SS) = C(SS)[1-(1/2)^n]

Question 8

What is the clinical steady state and what does it mean?

Answer 8

90% is the clinical steady state, and it takes 3.3 half-lives to reach it

this means that the full therapeutic effect will not be seen for 3.3 times the half-life

Question 9

ideal therapeutic regimen

Answer 9

maintains effective concentrations

minimize concentration variability, thereby avoiding toxic and subtherapeutic concentrations

minimize total dose

Question 10

idealized loading dose

Answer 10

depends on the target concentration adn the volume in which the dose is being diluted

C(SS) = Dose/V(d)

Dose = C(SS) x V(d)

Question 11

therapeutic objective

Answer 11

to maintain therapeutic, non-toxic drug concentrations at the sites of action

Question 12

factors affecting rate and extent of orally administered drug absorption

Answer 12

rate of disintegration

rate of dissolution

rate of absorption

transit time

first pass metabolism

Question 13

What happens to hepatic extraction ratio and elimination clearance when a drug with high hepatic extraction ratio is coupled with increased hepatic blood flow?

Answer 13

no change in hepatic extraction ratio and increased elimination clearance

Question 14

What happens to hepatic extraction ratio and elimination clearance when a drug with high hepatic extraction ratio is coupled with decreased hepatic blood flow?

Answer 14

no change in hepatic extraction ratio and decreased elimination clearance

Question 15

What happens to hepatic extraction ratio and elimination clearance when a drug with low hepatic extraction ratio is coupled with increased hepatic blood flow?

Answer 15

decreased hepatic extraction ratio, no change in elimination clearance

Question 16

What happens to hepatic extraction ratio and elimination clearance when a drug with low hepatic extraction ratio is coupled with decreased hepatic blood flow?

Answer 16

increased hepatic extraction ratio and no change in elimination clearance

Question 17

bioavailability

Answer 17

defined as F, fraction of the dose administered extravascularly that reaches the systemic circulation

by definition F_IV = 1 and Cl_E = Dose_IV/AUC_IV

when F_EV < 1, Cl_E = F_EV x Dose_EV/AUC_EV

Question 18

equation for extravascular bioavailability

Answer 18

F_EV = (AUC_EV/AUC_IV) x (Dose_IV/Dose_EV)

Question 19

bioavailability and absorption rate

Answer 19

absorption rate is going to limit the ability to produce therapeutic concentrations of the drug

peak concentrations are achieved later, and concentrations are maintained above threshold only for a short duration