Topic 2

Question 1

Absorption (Systemic)

Answer 1

• Passage of compound from the site of administration into bloodstream (usually across a membrane)
• Drug at absorption site -> absorption -> drug in body -> elimination

Question 2

Extravascular Administration

Answer 2

Refers to any route other than directly into the bloodstream (intravascular)

Question 3

Bioavailability

Answer 3

Refers to the rate and extent of absorption of intact drug; refers to the fraction of an extravascularly administered dose that reaches the systemic circulation intact

Question 4

Absolute Bioavailability

Answer 4

Based on the ratio of plasma (AUC) or urine (Ae(∞)) of an extravascular dose (ev) to an intravenous dose (iv)

Question 5

Relative Bioavailability

Answer 5

• Comparison of the bioavailability between formulations or a drug given either by the same or different routes of administration (i.e. oral tablet vs. intramuscular solution)
• Used when no intravenous formulation is available or when only comparative information is needed

Question 6

Bioequivalence

Answer 6

• Formulations containing the same dose of same chemical entity, generally in the same dosage form, intended to be interchangeable
• (i.e. clinical trials or generic substitution)
• Bioequivalent preparations are considered to be therapeutically equivalent
• To be bioequivalent, a test preparation should differ by no more than some small degree (usually 20%) in exposure profile

Question 7

Perfusion (BF) Rate Limitation

Answer 7

• Small lipophilic molecules (many drugs) passing across most membranes, or very small hydrophilic ones readily passing through pores/channels between cells or some membranes
• The membrane offers no effective barrier to drug molecule, and absorption rate varies with rate of blood flow

Question 8

Membrane Permeability Rate Limitation

Answer 8

• Seen with polar hydrophilic compounds moving across many membranes, e.g., intestinal tract
• Poorly permeable, with rate limitation lying with membrane
• Insensitive to changes in blood flow

Question 9

Gastric Emptying

Answer 9

-All drugs in solution are absorbed faster from intestine than stomach, irrespective of pH
• Any factor affecting the rate of gastric emptying may influence the systemic kinetics of the drug when given orally either in solution or in a solid dosage form

Question 10

INCOMPLETE ABSORPTION

Answer 10

-Lack of time: for dissolution (of sparingly soluble drugs), for release (from some controlled-release products), for membrane permeation (e.g., polar drugs)
• particular problem for drugs given orally
-Competing Reaction: instability (gastric pH); substrate for intestinal enzymes or microflora; complexation
–Hepatic and Gut Wall Extraction (more detail in other card)

Question 11

ENTEROHEPATIC CYCLING

Answer 11

• Some drugs are highly concentrated in the bile
• Due to active transport from the sinusoids of the liver to the bile canaliculi across the hepatocyte
• For a drug to be highly secreted into the bile it must be a substrate for the secretory mechanism
• Glucuronides that are polar/ionized/high MW(over300) are highly excreted into the bile
• CYCLE: Drug goes from liver to bile (stored in gb), gallbladder to intestine (until gb is emptied by effect of food), intestine to portal circulation

Question 12

If administered compound is a prodrug…

Answer 12

(without activity), bioavailability is frequently based on measurement of active metabolite, in which case the intravenous reference is the active metabolite

Question 13

Rate Limiting Steps in Absorption

Answer 13

• Absorption of drug from in a solution: Movement through membranes (lipid bilayers)
• Transcellular permeation either by passive diffusion, active transport or passive facilitated transport.
• Paracellular transport is always passive.

Question 14

Drug Release from Solid Formulations

Answer 14

solid drug -> release -> drug in solution -> entry into body -> absorbed drug

Question 15

Enterhepatic Cycling can have major impact on plasma concentration time-profile…

Answer 15

(EX.) This drug clearly shows slow release from the intact tablet and shows enterohepatic cycling as evidenced from the second peak in the concentration-time profile when food is taken 2 hours after the tablet

Question 16

Hepatic and Gut Wall Extraction

Answer 16

• under incomplete absorption (for GI tract)
• low bioavailability occurs for drugs that, when given orally, exhibit a high hepatic extraction ratio or are extensively metabolized in the gut wall. This is called the First-Pass Effect.