Block E Lecture 3: Drug Absorption and the Industrial Impact of Pharmacokenetics

Question 1

What are 3 examples of routes of drug administration?

Answer 1

Answers Include:
Intravenous
Intramuscular
Inhalation
Tropical / Subcutaneous (through the skin)
Rectal
Oral
(Part 1, Slide 3)

Question 2

Is bioavailability the same for each method of administration?

Answer 2

No
(Part 1, Slide 4)

Question 3

What is the barrier to absorption in oral drug administration?

Answer 3

Gastrointestinal mucosa
(Part 1, Slide 5)

Question 4

What are the barriers of absorption in tropical /subcutaneous drug administration?

Answer 4

Skin epithelium and subcutaneous tissues
(Part 1, Slide 5)

Question 5

What are 5 drug factors which affect the rate and extent of drug absorption?

Answer 5

Molecular size
Lipid solubility
Ionisation (charge) at physiological pH
Chemical form
Pharmaceutical nature of the drug
(Part 1, Slide 5)

Question 6

What are 3 patient factors which affect the rate and extent of drug absorption?

Answer 6

Surface area of the absorptive surface
Blood flow to the site of absorption
Stomach emptying and intestinal transit (for drugs given orally)
(Part 1, Slide 5)

Question 7

What is penetration rate?

Answer 7

The rate at which something can penetrate / permeate a barrier
(Part 1, Slide 6)

Question 8

What are 3 factors which affect a drug’s penetration rate for it to cross a barrier from the outside to the inside of the body?

Answer 8

Surface area
Concentration gradient
Lipid-solubility
Molecular weight
Membrane thickness
(Part 1, Slide 6)

Question 9

How do orally taken drugs find their way to their area of action?

Answer 9

1. Solid dosage form is taken orally
2. Disintegration of the dosage form occurs (not needed for capsules)
3. Drug particles dissolve (only soluble material may be absorbed)
4. Dissolved drug particles are absorbed across the membrane (into the blood)
   (Part 1, Slide 10)

Question 10

How does the form of the drug affect the pharmacokinetic profile?

Answer 10

Liquid / solution drugs have a high absorption which dissipates quickly.
Modified release tablets have a low absorption which dissipates slowly
Immediate release tablets are somewhere inbetween
(Part 1, Slide 11)

Question 11

What must occur before a drug is tested in humans?

Answer 11

Extensive testing using cell culture models and preclinical animal testing
(Part 2, Slide 2)

Question 12

What does extensive testing using culture models and animal testing do?

Answer 12

Predict or measure pharmacokinetic properties of a new drug
(Part 2, Slide 2)

Question 13

What is an IND?

Answer 13

It stands for investigation new drug document and it is meant to give an idea about the potential of a new substance as a drug
(Part 2, Slide 3)

Question 14

What 4 types of reports does an IND cover?

Answer 14

All reports dealing with:
Preclinical studies
Chemistry, manufacturing and controls (CMC)
Protocols for clinical studies
Investigational plan for clinical development (at least for year 1)
(Part 2, Slide 3)

Question 15

What are the 4 most important sections of an IND?

Answer 15

Details on pre-clinical animal studies + pharmacokinetics which support the clinical program and underpin toxicity assessment

Justification of clinical testing in humans (animal data which is used to understand how ADME and pharmacokinetic data will translate into humans)

In vitro models that predict specific aspects of pharmacokinetics

In silico (computer) models that predict overall pharmacokinetics in humans and integrate the impact of patient diversity
(Part 2, Slide 4)