L13 - optimising drug properties to ensure good oral bioavailability

Question 1

7 requirements for a good drug

Answer 1

1. efficacy
2. chemical stability
3. solubility
4. suitable LogP value (around 1 to 3)
5. oral bioavailability (not essential)
6. appropriate pharmacokinetics
7. favourable safety profile

Question 2

what does it mean by drugs need to have efficacy?

Answer 2

• Must give intended therapeutic effect
• Appropriate size and structure to interact with target

Question 3

what does it mean by drugs need to have chemical stability?

Answer 3

need to be stable over entire shelf life (not degraded by heat/light)

Question 4

what does it mean by drugs need to be soluble?

Answer 4

drug needs to be in solution to be absorbed

Question 5

what does it mean by drugs need to have a LogP value of 1 to 3?

Answer 5

needs lipophilicity

Question 6

what does it mean by drugs need to have good oral bioavailability?

Answer 6

..

Question 7

what does it mean by drugs need to have appropriate pharmacokinetics?

Answer 7

absorption, distribution, excretion, metabolism needs to be appropriate

Question 8

what does it mean by drugs need to have a favourable safety profile?

Answer 8

don’t want toxic drug that makes patient ill

Question 9

what is fick’s first law of diffusion?

Answer 9

J = A D K (Co - Ci) / h

Question 10

what does everything stand for in the fick’s first law equation?

Answer 10

J = flux / rate of absorption of a drug
A - membrane area
D = diffusivity of drug in memb
K = partition coefficient / lipophilicity of drug
(Co - Ci) = concentration gradient (change in C)
h = membrane thickness

Question 11

key points about ficks first law

Answer 11

• Larger the particle, smaller the diffusivity, decreasing flux/ rate of absorption
• Large conc gradient increases flux
• Partition coefficient is lipophilicity of drug
• Higher lipophilicity = greater absorption of drug
• Describes drug diffusion ACROSS A MEMB
• Applied to diffusion rate (flux) across whole
• epithelium (considering A and h)
• Properties of the drug are k, change in C and radius (MW)