Week 2 - Pharmacokinetics After I.V. Bolus (Plasma)

Question 1

KEY INFO

Answer 1

• Measure drug conc. in plasma (more than in blood) as its easier to isolate plasma / gain plasma data
• Rarely measure conc. at site of action
• AIM is to design drug that reaches optimal plasma conc. = reaches therpeutic conc. at site of action = therpeutic effect
• ADME process (metabolism + excretion are both elimination processes)

Question 2

KEY INFO RELATING TO IV ADMINSTRATION

Answer 2

• IV gives complete adminstration (bypass 1st pass metabolism)
• Bioavailabilty (F) for IV = 1
• With IV dont need to consider absorption factor, 1st pass metabolism
• IV infusion is given over short period of time

Question 3

What are the 2 phases following IV bolus dose

Answer 3

Phase 1 = Distribution
- drug is distributing from plasma to tissue
- occurs faster in highly perfused tissues
- time for drug in tissue to reach equilibirum with drug in plasma
- phase is shown at start of graph (rapid decline as drug is leaving blood)
- fraction of dose eliminated is very small here

Phase 2 - Elimination (terminal)
- at this stage we’ve reached equilibirum
- phase is shown in second half of graph (gradual decline as drug leaves body i.e. metabolism or excretion)
- elimination rate constant (k) and elimination half life (t1/2)= parameters assoictaed

Question 4

Define elimination rate constant

Answer 4

The fractional rate of drug loss
(i.e. how quickly drug is eliminated per unit if time)

High k = faster elimination
UNITS = min-1 OR h-1

Question 5

Define elimination half life (t1/2)

Answer 5

Time taken for plasma drug conc to fall by half (once distribution equilibrium has been achieved)

Question 6

What 3 parameters can be calculated from the AUC

Answer 6

1. Clearnace (Cl)
   - CL = D ÷ AUC
   - D = dose
2. Elimination rate constant (k)
   - calculated from slope (on graph)
3. Volume of distribution (V)
   - D ÷ (k x AUC)

Question 7

Define what a first-order process is

Answer 7

Rate of process is directly proprotional to drug plasma conc.
- i.e. higher drug conc. = higher rate

Rate = k x C
C = conc.
negative sign (-k) as conc. is decreasing

Question 8

How to calculate inital conc. (C0) from plasma conc. following an IV bolus dose

Answer 8

C(0) = D ÷ V

C(0) = inital conc
Ct = conc. at any given time
D = dose
V = vol. of disribution

Question 9

How to calculate total clearance from plasma conc. following an IV bolus dose

Answer 9

Cl = k x V

Question 10

How to calculate volume of distribution (V) from plasma conc. following an IV bolus dose

Answer 10

V = D ÷ C(0)

C(0) = intial conc.
D = dose

Question 11

How to calculate elimination half-life (t1/2) from plasma conc. following an IV bolus dose

Answer 11

t1/2 = ln2 ÷ k
k = elimination rate constant (slope of graph from phase 2 ~ gradual decline)
ln2 (log2) = 0.693

OR

t1/2 = (0.693 x V) ÷ Cl
- V and Cl influence t1/2
- if change dose BUT same drug Cl, V and t/12 should NOT change

Drug with short t1/2 = drug will be eliminated quicker
- Takes 3.3 t/12 to eliminate 90% of drug / 10% of dose remianing
- classed as complete elimination

Question 12

How to calculate elimination rate consant (k) from plasma conc. following an IV bolus dose

Answer 12

k = Cl ÷ V

Question 13

How to calculate the drug conc. in plasma with the time following an IV bolus dose