Week 8 - Phamacokinetics Following an Extravascular Dose

Question 1

How does the absorption process contribute to plasma conc-time profile following an extravascular route of drug adminsitration

Answer 1

How does the plasma-conc profile differ to IV bolus plasma conc.
- conc. starts at 0 gradually increases till reaches a peak (drug moving into plasma)
- IV bolus starts at high conc.
- increases as absorption is dominating
- sometimes have tlag (lag time) = delay between administration of drug + drug appearance in plasma / systemic circulation
- After peak, conc. declines (elimination dominatating)

HARD to tell if profile is absortion limited or elimination limited = COMPARE profile to IV profile (always elimination limited ~ terminal phas)

With extravscular administartion need to consider:
- Disintegration
- Dissolution
- Absorption
- Permeability
- 1st pass metabolism (loss / delay of drug in gut and liver)

ALL occur before dug reaches site of measurement (from its site of administration)

Question 2

How to calculate Clearance (CL) following extravascular dosing

Answer 2

(F x D) / AUC

F = bioavailabilty
D = dose

CL is the same whether drug is administered IV or EV

Question 3

How to calculate Volume of distribution (V) following extravascular dosing

Question 4

How to calculate Elimination half-life (t1/2) following extravascular dosing

Answer 4

t1/2 = ln2 / k

ln2 = 0.693

Question 5

How does changes in Bioavailabilty (F) affect plasma-conc. profile

Answer 5

As increase F:
- Cmax will increase
- AUC will change
- Tmax will remain SAME

Question 6

What is ka and how does changing ka affect the plasma-conc. profile

Answer 6

ka = rate of absorption

IF ↓ ka:
- Cmax will ↓
- Tmax will ↑
- AUC remains unchanged

Question 7

What is dissolution rate-limited absorption

Answer 7

Slow dissolution BUT high permeability
- when drug dissolves + gets into solution will cross intestinal wall + be absorbed

PROBLEM: drug takes time to disintegrate + appear in solution

Question 8

What is permeability rate-limited absorption

Answer 8

Rapid dissolution BUT low permeability
- drug disintegrates + appears in solution quickly

PROBLEM: is drug crossing the membrane
- unable to cross intestinal wall + get absorbed
- delay in drug trasfer from absorption site to site of measurement