L6 Quantitative Pharmacokinetics

Question 1

Fu equation gives

Answer 1

The fraction of drug unbound in plasma

Question 2

The plasma concentration-time curve - what info does it give us

Answer 2

• dose
• frequency of drug administration
• toxicity

Question 3

Routes of administration

Answer 3

Intravenous and oral

Question 4

Therapeutic window

Answer 4

a concentration range bounded at the lower end by the minimum concentration that produces the desired clinical effect and at the upper end, the concentration that produces unacceptable effects or where no further benefit is observed.

Question 5

In a plasma concentration-time curve what is C(max), T(max) and AUC

Answer 5

• Cmax - peak plasma concentration
• Tmax - the time required to achieve Cmax
• area under the curve

Question 6

minimum toxic concentration (MTC)

Answer 6

the upper limit of the therapeutic window. Drug concentrations above the MTC increase the risk of undesired effects

Question 7

Minimum effective concentration (MEC)

Answer 7

the plasma drug level below which therapeutic effects will not occur

Question 8

First- and zero-order kinetics

Answer 8

First- and zero-order kinetics refers to changes in the amount of drug in the body as a function of time

Question 9

First-order kinetics [def]

Answer 9

change by a constant fraction per unit time

Question 10

Zero order kinetics [def]

Answer 10

Change by a constant amount per unit time

Question 11

First-order kinetic

Answer 11

elimination of most drugs follows first order kinetics
- clearance and half-life are constant
- constant fraction of drug is eliminated per unit time
- can change from first order to zero order as the drug concentration increases and elimination mechanisms become saturated

Question 12

The larger the margin inbetween the MTC and MEC is better or worse for drugs

Answer 12

better

Question 13

Zero-order kinetics

Answer 13

• drugs are removed at a constant rate which is independent of plasma concentration
• elimination of a few drugs (e.g., alcohol*ethanol bc of al) follows zero-order kinetics
• all the active sites on an enzyme or transporter are occupied - saturated elimination mechanisms

Question 14

Plasma-conc graph I.V and oral drug conc starts where

Answer 14

I.V - 1
Oral - 0

Question 15

Drug clearance

Answer 15

Drug clearance refers to the efficiency of drug elimination, defined as the ratio of the elimination rate (e.g., mg∙h-1 ) to the concentration of drug in plasma (e.g., mg∙L-1 )

Question 16

total body clearance =

Answer 16

total body clearance = hepatic clearance + renal clearance + clearance by other routes

Question 17

[clearance by a specific organ]; renal clearance =

Answer 17

renal clearance = glomerular filtration + active secretion - reabsorption

Question 18

fe

Answer 18

• the fraction of administered drug
  excreted unchanged in the urine

Question 19

What clearance if low fe

Answer 19

hepatic clearance bc metabolites excreted

Question 20

What clearance if high fe

Answer 20

Renal clearance bc parent drug is excreted

Question 21

Drug bioavailability

Answer 21

Drug bioavailability (F) is the fraction of administered dose of the parent drug that reaches the systemic
circulation

Question 22

First order kinetic graphs [1IV]

Answer 22

plasma-time = curved graph
- also be straight if natural/inverse log

Question 23

Zero order kinetic graph [1IV]

Answer 23

Straight graph

Question 24

Enzyme of ethanol

Answer 24

Alcohol Dehydrogenase

Question 25

is Alcohol Dehydrogenase easily saturated

Answer 25

yes

Question 26

Drug bioavailability must be given in

Answer 26

fraction or percentage

Question 27

bioavailability of an orally administered drug
* obtain plasma concentration-time curve of the drug via ____ and ___routes

Answer 27

i.v. and oral

Question 28

Determine total body clearance in NCA

Answer 28

a simple approach to determine (Cltotal) in NCA
- administer a single dose of drug (i.v. bolus or oral)
- collect blood samples and measure drug plasma concentration at defined time points
- plot a plasma concentration-time curve, and calculate the AUC

Question 29

Compartmental (requires___) or non-compartmental analysis (___)

Answer 29

modelling
NCA

Question 30

Use the___ method to calculate AUC

Answer 30

trapezoidal

Question 31

elimination rate constant (k)

Answer 31

the slope of the ln[plasma concentration]-time curve for drugs that follow
first-order kinetics - indicates the fraction of a drug removed per unit time

• CL(total) / -V(d)

Question 32

drug elimination half-life (t1/2)

Answer 32

the time taken for the drug plasma concentration to decrease by 50% and is calculated during the elimination phase
- CL(total) and -V(d)

Question 33

steady-state concentration [def]

Answer 33

steady-state concentration is the concentration of drug in the plasma reached when the rate of drug absorption is equal to the rate of drug elimination following repeated or continuous dosing

Question 34

How to get higher steady-state concentration

Answer 34

higher doses and/or more frequent dosing will result in higher steady-state concentrations

Question 35

steady-state concentration-to achieve clinical response rapidly:

Answer 35

loading dose (=
Vd × target plasma-concentration) followed by
maintenance dose

Question 36

drug elimination half-life (t1/2) is proportional to ___ and inverse proportional to __

Answer 36

1. V(d)
2. CL(total)

Question 37

increased Vd, e.g., in pregnancy [and]
decreased Cltotal, e.g., liver/kidney disease lead to what

Answer 37

an increase in drug elimination half life.