Absorption and Half Life

Question 1

What are the two components of absorption?

Answer 1

Extent of absorption (total amount of drug in body-not time dependent)
Rate of absorption (how quickly drugs enters the body)

Question 2

What are the two components of extent of absorption?

Answer 2

Fraction of drug absorbed and first pass extraction

Question 3

What is fraction of drug absorbed?

Answer 3

Drug that gets into the portal vein from the gut. Small unionised molecules are completely absorbed (theophylline). Large ionised molecules have difficulty and only 5% cross the gut wall (gentamicin)

Question 4

What is first pass extraction?

Answer 4

Fraction of drug removed while passing liver which relates to intrinsic organ clearance and blood flow. High blood flow to liver = first pass extraction is low. High intrinsic clearance = first pass extraction is high

Question 5

What is the overall extent of absorption?

Answer 5

Bioavailability
F = f . (1-ER)
f is fraction absorbed across gut
ER is hepatic extraction ratio

Question 6

What are the three possible input processes?

Answer 6

Bolus (intra venous injection) -instantaneous absorption
Zero order (constant rate IV infusion) -absorption constant for a period of time
First order (intra muscular injection) -absorption is proportional to amount of drug at absorption site

Question 7

What determines the rate of a zero order absorption?

Answer 7

Tmax: The stomach emptying time (physiological control)
Tk0: Slow release formulation (pharmaceutical control)

Question 8

What determines the rate of a first order absorption?

Answer 8

Intestinal absorption (KA)
Diffusion limited
Absorption half life can be calculated by 0.7/KA
Absorption complete after 4 half lives

Question 9

What are the applications of understanding absorption?

Answer 9

IV to oral dose conversion

Time to peak concentration

Question 10

What are the three components of half life?

Answer 10

Absorption
Elimination
Accumulation

Question 11

What is the formula for half life?

Answer 11

T1/2 = (0.7 x Volume of distribution)/ Clearance

Question 12

How are elimination and accumulation related?

Answer 12

Inverse of each other

Question 13

How does accumulation affect dosing?

Answer 13

All dosing methods accumulate at the same rate as constant rate infusion

Question 14

What is accumulation factor?

Answer 14

The ratio of the concentration at steady state to the concentration after the first dose at the same time after the dose. If dosing interval is equal to the half life then the accumulation factor is 2

Question 15

When is peak concentration?

Answer 15

3 times absorption half life