2 - Drug Absorption & Bioavailability

Question 1

What is bioavailability?

Answer 1

Fraction of the drug that reaches the systemic circulation unchanged

Question 2

Where is the majority of a drug absorbed?

Answer 2

Small intestine

Question 3

Are drugs absorbed substantially in the stomach? Why or why not?

Answer 3

• No

- Acidic drugs are unionized in the stomach, but aren’t absorbed b/c thick mucous layer and thick gastric wall

Question 4

Function of P-glycoprotein

Answer 4

Pump that pushes substances foreign to the body back into the GI lumen and prevents its absorption

Question 5

How do you calculate absolute bioavailability?

Answer 5

F = (AUC po / dose po) / (AUC IV / dose IV)

Question 6

How do you calculate relative bioavailability?

Answer 6

F = (AUC / dose for new formulation) / (AUC / dose for standard formulation)

Question 7

What is bioequivalence?

Answer 7

• Comparing relative bioavailability of the brand vs. generic drug
• No more than 20% difference between AUC’s and Cmax’s
• Mean ratio of the AUC and its respective 90% confidence interval should lie w/in the limits of 0.8 to 1.25; 1.0 = identical (Cmax should also lie w/in 0.8 to 1.25 but not its 90% confidence interval)

Question 8

What is bioequivalence for critical dose drugs?

Answer 8

• 90% confidence interval on the AUC ratio should lie w/in 0.9 to 1.12
• 90% confidence interval on the Cmax ratio should lie w/in 0.8 to 1.25

Question 9

What are some important factors governing the absorption of drugs?

Answer 9

• Molecular size and shape of drug and its concentration
• Lipid solubility of unionized form of the drug
• Chemical or physical interactions w/ other drugs or food
• Characteristics of the dosage form (disintegration and dissolution)
• Fluid volume in GI tract
• Osmolality of intestinal contents

Question 10

Location of P-glycoprotein

Answer 10

Apical surface of epithelial cells in liver, kidney, brain capillaries, placenta, and GI tract

Question 11

Is p-glycoprotein an example of passive or active transport?

Answer 11

• ATP dependent, so active transport

- Able to pump against a concentration gradient

Question 12

Describe the drug interaction between dabigitran and verapamil

Answer 12

• If verapamil given 1h prior to dabigitran, bioavailability of dabigitran will increase dramatically b/c verapamil is P-gp inhibitor
• If dabigitran given 2h prior to verapamil, no interaction

Question 13

What does it mean when a drug is a P-gp inducer?

Answer 13

Absorption of other drugs will be decreased b/c P-gp will be preventing absorption

Question 14

What does it mean when a drug is a P-gp inhibitor?

Answer 14

Absorption of other drugs will be increased b/c P-gp isn’t preventing the absorption

Question 15

Describe the drug interaction between dabigitran and rifampin

Answer 15

Rifampin is a strong P-gp inducer, so decreases absorption of dabigitran

Question 16

Describe the drug interaction between digoxin and amiodarone

Answer 16

Amiodarone = P-gP inhibitor, so absorption of digoxin increases by 100%

Question 17

Describe the drug interaction between digoxin and rifampin

Answer 17

Rifampin = P-gP inducer, so decreases digoxin absorption by 30%

Question 18

How can you assess whether patients have adequate GI function?

Answer 18

• Presence/ absence of bowel sounds
• Absence of diarrhea, nausea, or constipation
• Tolerance of diet or tube feedings

Question 19

How can you assess if the stomach is emptying and nutrients and drugs are being absorbed?

Answer 19

• Acetaminophen absorption testing

- Not absorbed in the stomach but completely absorbed in the small intestine

Question 20

Is acetaminophen affected by CYP 3A4 or P-gP?

Answer 20

No

Question 21

What is the method of administration for acetaminophen absorption testing?

Answer 21

• Administer 650 mg of acetaminophen (975 or 1000 mg in pt over 90 kg) ideally as liquid product
• Measure plasma levels at 0.5, 1, and 2 hours after dose
• Determine AUC
• Compared this value w/ a weight-adjusted value for healthy volunteers

Question 22

What are some limitations to the acetaminophen absorption testing?

Answer 22

• Ensure no acetaminophen has been received for at least previous 12 h
• Severe liver dysfunction may prolong t1/2
• Assume Vd is fixed at 0.95 L/kg
• Can’t be assessed in the presence of lipemic serum
• Hyperbilirubinemia can cause false positives for acetaminophen