Week 3 - Pharmacokinetics Following a Constant Rate Infusion

Question 1

Define steady-state

Answer 1

When rate of input (from infusion) = rate of output (elimination)
- if have higher inpit = rate of elimination will equally begin to increase

Css = R0 ÷ CL
- R0 = rate of infusion

On Graph:
- without IV bolus dose at time 0 the conc. will be 0
- the plasma conc. gradually increases over time then begins to plateau
- CSS is when reach a plateau

Question 2

What factors 2 govern steady state

Answer 2

1. R0 = rate of input
2. CL= clearance

Css = R0 ÷ CL

If wat to change dose:
- If double R0 the Css will double (vice versa if decrease)
- If same patient CL will remian the same

Question 3

How to calculate amount of drug (A)

Answer 3

A = V x C

V = vol. of distribution
C = conc.

Question 4

What is constant infusion

Answer 4

• constant rate of drug delivery in order to reach a constant plasma conc.
• is a 0 order process (R0) as it’s a constant rate of drug delivery
  - R0 = rate of infusion
  GOAL: have a constant plasma conc. = constant therapeutic effect

Question 5

What 2 processes affect rate of change of drug in body (following infusion)

Answer 5

Rate is proprotional to:
1. k x A
- k = elimination rate constant
- A = amount of drug in body
AND
2. Cl x C

Question 6

What is the relationship between t1/2 and Css

Answer 6

The time to REACH Css solely DEPENDS on t1/2
- in 3.3 half lives 90% of steady state is assumed
- in 1 t1/2 = 50% and 2 t1/2 = 75%
- all drugs take 3.3 but the time taken varies

• if drug has longer t1/2 = time taken to reach Css is longer
• if drug has shorter t1/2 = time taken will be shorter

t1/2 determines:
- time it takes to reach Css
- time it takes to go from on steady state to another

Question 7

How do we quickly achieve relevant therpeutic plasma conc. and maintain it?

Answer 7

• Give bolus dose = loading dose
  = will reach high conc. immediately
  - loading dose = V x Css
• Follow with infusion = maintenance dose
  - will maintain the high conc. as the conc. from bolus begins to decrease
  - R0 = Css x CL

Will maintain Css if get loading dose and rate of infusion correct

Question 8

What is the relationship between t/12 of a drug and the time required to reach Css following a constant rate infusion (WITH initial bolus dose)

Answer 8

The time to REACH Css solely DEPENDS on t1/2

• Bolus dose is beneficial for drugs with long t1/2

Bolus Dose:
- reach high conc. of drug immediately (reach Css from beginning)
- as time progresses conc. begins to drop = therpeutic effect wears off

Question 9

What is the relationship between t/12 of a drug and the time required to reach Css following a constant rate infusion (WITHOUT initial bolus dose)

Answer 9

The time to REACH Css solely DEPENDS on t1/2

• Will take longer time to reach high conc. of drug / reach Css

Question 10

How do you estimate t1/2 from plasma conc. data following a constant rate infusion (also using urine data)

Answer 10

• From post infusion data (calcualte gradient of slope after stopping infusion)

Question 11

How do you estimate volume of distribution (V) from plasma conc. data following a constant rate infusion (also using urine data)

Answer 11

V = (CL x t1/2) ÷ 0.693

Question 12

How do you estimate clearance (CL) from plasma conc. data following a constant rate infusion (also using urine data)

Answer 12

CL = R0 ÷ Css
OR
CL = (R0 x τ) ÷ AUC
- τ = duration of infusion
- this equation doesnt require steady state

• Css measured needs to be the plateau cant be above or below this level

Question 13

How do you predict the plasma conc. with time during and after an IV infusion (WITH a bolus dose)

Question 14

How do you predict the plasma conc. with time during and after an IV infusion (WITHOUT a bolus dose)