Biopharmaceutics

Question 1

Define absolute bioavailability.

Answer 1

Fraction of a drug that enters the systemic circulation.

Question 2

What are the benefits of injectables?

Answer 2

Rapid response
Patient may be unconscious
Drug cannot be removed in vomiting
Good where drugs have limited oral bioavailability

Question 3

Which layer of the skin is the most impermeable and hardest to penetrate?

Answer 3

Stratum corneum

Question 4

What is the dermis?

Answer 4

Thick layer of tissue below the skin that is perfused by capillaries from deeper layer of arteries/veins in the hypodermis

Question 5

What is the stratum corneum?

Answer 5

Outer layer of dead cellular material

Question 6

What is the general transit time of the GIT?

Answer 6

12-36 hours

Question 7

What are the two sites of first pass metabolism?

Answer 7

Liver

Intestinal wall

Question 8

Describe the features of the stomach leading to minimal absorption.

Answer 8

Tight junctions between cells limit paracellular transport

Epithelial surface is smooth with low surface area

Question 9

Describe the features of the small intestine leading to maximal absorption.

Answer 9

Transit time is 3-4 hours
Large surface area
Highly perfused with 25% of cardiac output

Question 10

What is the splanchnic circulation?

Answer 10

Intestinal veins flow into portal vein

Blood rich in materials is filtered through hepatic sinusoids

Question 11

What is the transit time of the colon?

Answer 11

2-48 hours depending on frequency of defication

Question 12

Is there anything that affects transit time of the small intestine?

Answer 12

Independent of fed/fasted state

Question 13

What is the volume of the stomach?

Answer 13

50mL fasted

>1000mL fed

Question 14

What properties of neonatal GIT affects drug absorption/bioavailability?

Answer 14

Reduced acid secretion may increase bioavailability of acid labile drugs and increase solubility of acidic drugs

Question 15

List the age ranges of paediatrics.

Answer 15

Neonate 0-27 days
Infant 1-23 months
Child 2-11 years
Adolescent 12-18 years

Question 16

How does the expression of metabolising enzymes in the gut wall differ in paediatrics?

Answer 16

CYP3A expressed in 50% of children under 6 months

Question 17

How does the expression of metabolising enzymes in the liver differ in paediatrics?

Answer 17

CYPs generally present from birth, reaching adult levels by 2-5 years
UGTs reach adult levels anytime from 2 years

Question 18

What are the physiological changes that occur in children that can alter absorption and pharmacokinetics?

Answer 18

• saliva production
• gastric pH and emptying rate
• intestinal transit, SA and motility
• drug metabolising enzymes
• drug efflux transporters

Question 19

What is the general trend of pH along GIT as you get older?

Answer 19

pH decreases

Question 20

What effect does transit time have on paediatric formulations?

Answer 20

Irregular intestinal motility leads to variable transit times which can be a problem for controlled release formulations

Question 21

How is metabolism affected in paediatric patients?

Answer 21

Children have a larger liver size and hepatic blood flow per body weight so there is more 1st pass metabolism and increased clearance

Question 22

What is formulation bridging?

Answer 22

Assessing the rate and extent of absorption from one formulation vs. another