2.2:4 Absorption of drugs from the GIT: Bioavailability

Question 1

What is bioavailability and what are its 2 major aspects?

Answer 1

Fraction of administered dose reaching the systemic circulation in unchanged form

This depends on the rate and extend of absorption across the GI wall

Extent of drug metabolism or breakdown before it reaches the systemic circulation

F will always be less than 100%

Question 2

What causes loss in oral bioavailability?

Answer 2

Loss in faeces (drugs not absorbed or effluxed by P-glycoprotein)

Decomposition in the lumen

Destruction within the wall of the GIT (intestinal first pass metabolism)

Destruction within the liver (hepatic first pass metabolsim)

Question 3

Define the equation F = Ff x Fg x Fh

Answer 3

F- Bioavailabilty
Ff- Fraction entering the intestinal wall tissue
Fg- Fracyion that survives the distruction in the intestinal wall
Fh- fraction that survives the decrtuction in the liver

Therefore if 50% of drug is lost at each step 0.5 X 0.5 X 0.5 = 0.125 or 12.5%

Question 4

How would you calculate bioavailability bases on plasma concentration?

Answer 4

Compare bioavailability of oral administration to the bioavalability of the same drug intravenously

F= (AUCoral/AUCiv) x (Doseiv/Doseoral)

Assuming that clearance remains constant

Question 5

What is lipinskis rule of five?

Answer 5

Empirical rule that evaluates druglikeness or determins if a chemical compound has properties that would make it a likely orally active drug in humans

Question 6

According to lipinskis rule of 5, what are his rules?

Answer 6

1. Not more than 5 hydrogen bond donors (nitrogen or oxygen with one or more hydrogen atoms)
2. not more than 10 hydrogen bond acceptors (nitrogen or oxygen atoms)
3. A molecular mass less than 500 daltons
4. An octanol-water particion coefficient (logP) not greater than 5

Question 7

What are the biopharmaceutic classufucation system?

Answer 7

Class I: Highly sobility, High permeability
Class II: Low solubility, High permeability
Class III: High solubility, Low permeability
ClassIV: Low solubility, Low permeability

Question 8

True/false: A drug sunstance is considered highly soluble when the highest dose is soluble in 250ml or less of aqueous media over a pH of 1-7.5 at 37 degrees

Answer 8

True

Question 9

True/false: A drug substance is considere to be highly permeable when the extent of absorption in human is determined to be 90% or greater of administered odse based in mass balance determination

Answer 9

True