Pharmaceutics - PK

Question 1

What are the 2 ways that drug input (absorption) into the body can be rate limited?

Answer 1

Dissolution (release) rate limiting –> Normally XL drugs

Permeability rate limiting –> Normally drugs with poor solubility

Question 2

What type of absorption rate-limiting does this graph represent?

Answer 2

Permability rate-limiting

Because most of the drug is dissolved, and dissolution/release is fast

Question 3

What type of absorption rate-limiting does this graph represent?

Answer 3

Dissolution (rate)

This is because the dissolution/release is slow, and any drug that is dissolved is rapidly absorbed

Question 4

What is disposition?

Answer 4

Distribution + Elimination

Where the absorption of a drug occurs quicker than it is eliminated

The elimination rate constant determines the decline in plasma concentrations of the drug

Question 5

What is ‘Flip-Flop’ kinetics?

Answer 5

When absorption of the drug is slower than elimination

This means that most of the drug is either at the absorption site or has been eliminated (at any one time)

The decline of the termal phase is determined by the rate of absorption

Question 6

Which of the below formulations is the immediate one, and which one is sustained release?

Why?

Answer 6

A –> Sustained Release, because it takes longer to reach Cmax (greater Tmax), and the Cmax is lower

Also Beta (terminal phase constant) is smaller, with the absorption constant probably being greater (so elimination rate-limiting)

B –> Immediate Release, because Tmax is small and Cmax is high (as released rapidly and absorbed)

Beta is greater, and so probably bigger than the absorption rate constant, meaning that absorption is the limiting step)

Question 7

What are the 2 types of metabolism that can occur? (in terms of metabolites)

Answer 7

Parallel

Sequential

Question 8

Here, what is the drug elimination rate equal to?

Answer 8

The rate of metabolite formation

This is because it is a single elimination pathway

Question 9

Here, what is the rate of metabolite formation equal to?

Answer 9

Question 10

What are the 2 types of rate-limiting that can occur in terms of metabolite elimination?

Answer 10

Formation rate-limited –> Occurs when the metabolite is eliminated faster than the parent compound (due to being more water soluble for example)

The terminal phase slope represents K

Elimination rate-limited –> When the metabolite is eliminated slower than the parent drug (best for pro drugs)

The terminal phase is controlled by the metabolite elimination, so mimicks kME

Question 11

Match the cases to the graph

Answer 11

Case 1 –> Graph A

Because the drugs elimination controls the metabolite

Case 2 –> Graph B