Pharmacokinetics

Question 1

• Administration regimens using Vensim: (3)

Answer 1

– STEP function
– PULSE function
– PULSE TRAIN function

Question 2

What is pharmacokinetics? (3)

Answer 2

• Branch of pharmacology
• Rates at which drugs are:
– Absorbed
– Distributed 
– Metabolised 
– Eliminated
• How drugs move within the body

Question 3

• So far we’ve considered rates that are
– Constant
– Exponential
– Always started at time zero
However, drug administration regimens… (2)

Answer 3

– Not always constant

– Don’t always start at time zero

Question 4

• In Vensim we have a set of functions:

Answer 4

– STEP function
– PULSE function
– PULSE TRAIN function

NOTE: Dose = rate x duration

Question 5

What does the graph for a constant rate for a ZOS look like?

Answer 5

Question 6

What is a step function?

Answer 6

• Constant rate 
– ZOS
• Step Function
– Does not start at zero
• Application
– Intravenous drip

Question 7

How do you work out the step?

Answer 7

Question 8

What are the applications of a pulse function?

Answer 8

1. Bolus injection
   • Single large dose delivered over a short period
   • Generally given when patient requires meds immediately in bloodstream
2. Ingesting a single dose of drugs
   • A pill or multiple pills taken over a short period
   • e.g. Analgesia (pain killers)

Question 9

A pulse function is not ____.

Answer 9

repeated

Question 10

What does the graph for a pulse function look like?

Answer 10

Question 11

What is the area under the rate curve of the pulse function?

Answer 11

𝐴𝑟𝑒𝑎 𝑢𝑛𝑑𝑒𝑟 𝑅𝑎𝑡𝑒 𝑐𝑢𝑟𝑣𝑒 = h𝑒𝑖𝑔h𝑡 ∗ 𝑑𝑢𝑟𝑎𝑡𝑖𝑜𝑛

Question 12

The area under Rate curve of pulse function =

Answer 12

Change in Level (Dose)

Question 13

What is the formula for the dose of a pulse function?

Answer 13

𝐷𝑜𝑠𝑒 = h𝑒𝑖𝑔h𝑡 ∗ 𝑑𝑢𝑟𝑎𝑡𝑖𝑜𝑛

Question 14

What is the formula for the height of a pulse function?

Answer 14

1 h𝑒𝑖𝑔h𝑡 = 𝐷𝑜𝑠𝑒 ∗ 1/𝑑𝑢𝑟𝑎𝑡𝑖𝑜𝑛

Question 15

What are the applications of a pulse train function?

Answer 15

1. Series of bolus injections
   • Repeated single large doses delivered over short periods
2. Ingesting a single dose of drugs at regular intervals
   • A pill or multiple pills taken over a short period
   • e.g. Antibiotics; hormone replacement drugs

Question 16

Consistent time between ___ for a pulse train function.

Answer 16

doses

Question 17

What is the pulse train function graph?

Answer 17

Question 17

What is the pulse train function graph?

Answer 17

Question 18

What is the function equation?

Answer 18

height * PULSE TRAIN ( start , dur , rt , end )

Question 19

What is the importance of a time step? (2)

Answer 19

• Extremely important with pulses

* Too large and you can miss pulse completely

Question 19

What is the importance of a time step? (2)

Answer 19

• Extremely important with pulses

* Too large and you can miss pulse completely

Question 20

In Vensim, dose = ____.

Answer 20

Dose = rate x duration

Question 21

What is the importance of modelling of a single compartment model? (3)

Answer 21

– Simplifying assumption
– Makes analysis easier
– Modelling the body as one single compartment

Question 22

What are the units of the auxiliary variable?

Answer 22

Question 23

What is clearance? (3)

Answer 23

• Important concept in system dynamics • Dimensional consistency but there is a slightly more subtle meaning • Allows us to use: – Concentration of drug instead of the absolute amount of drug – FOS elimination

Question 24

What type of value is clearance and what is the equation for clearance? (2)

Answer 24

• Clearance is a constant value – Characteristics of a FOS – Modified version of rate constant (k) SCALED by Volume of Distribution (V) 𝑐𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 = 𝑘 ∗ 𝑉

Question 25

How would the clearance variable appear on an LRD?

Answer 25

Question 26

What is the formula for the amount of the drug (level) ?

Answer 26

𝐴 = ∫ 𝐴𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑟𝑎𝑡𝑖𝑜𝑛 − 𝐸𝑙𝑖𝑚𝑖𝑛𝑎𝑡𝑖𝑜𝑛 𝑑𝑡

Question 27

What is the formula for the concentration of the drug?

Answer 27

Level/Volume

Question 28

What is the formula for clearance?

Answer 28

𝑐𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 = 𝑘 ∗ 𝑉

Question 29

What is the formula for the elimination rate?

Answer 29

𝐸𝑙𝑖𝑚𝑖𝑛𝑎𝑡𝑖𝑜𝑛 = 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 ∗ 𝑐𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒

Question 30

What are the characteristics of administration? (2)

Answer 30

• Administration – Repeats at regular intervals (PULSE TRAIN) height * PULSE TRAIN ( start , dur , rt , end )

Question 31

For administration: – start = 10 hours = _____ {minutes} – dur = 6 seconds = _____ {minutes} – rt = 12 hours = _____ {minutes}

Answer 31

= 10 * 60 = 6 / 60 = 12 * 60

Question 32

``` • Administration – end: • 3 days, twice daily is 6 doses total • Must account for the start time and duration to ensure all 6 doses are accounted for – end = __________________________. ```

Answer 32

= (10*60) first dose + (5*12*60) time for remaining doses + (6/60) duration {minutes}

Question 33

• Administration – height: • Administration is a rate, and the dose is an amount! • Assume the dose is evenly administered over the duration of each pulse height = ______________.

Answer 33

h𝑒𝑖𝑔h𝑡 = 𝐷𝑜𝑠𝑒 ∗1/𝑑𝑢𝑟𝑎𝑡𝑖𝑜𝑛 – height = 500 * (60/6) {mg/min}

Question 34

What does the full graph for a pulse train function look like?

Answer 34