Pharmacokinetics

Bioavailability (F) - Fraction of the administered dose that reaches systemic circulation unchanged (compared with IV).

First-pass metabolism - Drug metabolism in gut wall and/or liver before systemic circulation (reduces F for oral dosing).

Absorption rate - Speed at which drug enters systemic circulation (affects onset and early plasma levels).

Onset of action - Time until drug concentration at the site of action reaches the effective level.

AUC (Area Under the Curve) - Overall systemic exposure; lower F generally gives lower AUC after non-IV dosing.

Permeability - Ability of drug to cross biological membranes (limits absorption for polar drugs).

Active Recall

Absorption - __________________________________________________

__________________________________________________

__________________________________________________

Bioavailability (F) - __________________________________________________

__________________________________________________

__________________________________________________

First-pass metabolism - __________________________________________________

__________________________________________________

__________________________________________________

Absorption rate - __________________________________________________

__________________________________________________

__________________________________________________

Onset of action - __________________________________________________

__________________________________________________

__________________________________________________

AUC (Area Under the Curve) - __________________________________________________

__________________________________________________

__________________________________________________

Permeability - __________________________________________________

__________________________________________________

__________________________________________________

Worked Examples

Example 1 (Straightforward): IV vs Oral onset

A 50 mg dose is given IV and oral (same drug). Assume elimination is identical and the oral route has F = 0.5.

• IV: F = 1, so systemic exposure is higher immediately.

• Oral: only 50% reaches systemic circulation unchanged.

• Onset: oral onset is often delayed because drug must be absorbed first, and exposure may be lower, potentially delaying reaching the effective concentration.

Now you try

A 100 mg oral dose has F = 0.25. The same drug is given IV at 50 mg.

__________________________________________________

__________________________________________________

__________________________________________________

__________________________________________________

Example 2 (Rate vs extent): formulation changes absorption rate

Two oral formulations deliver the same dose and have the same F. Formulation A absorbs faster than B.

• Same F → similar overall AUC (extent).

• Faster absorption rate → earlier rise in plasma concentration.

• Onset: A should show earlier onset than B even though total exposure is similar.

Now you try

Formulation A and B have the same F, but A has faster absorption. Predict which one shows earlier onset and why.

__________________________________________________

__________________________________________________

__________________________________________________

__________________________________________________

Example 3 (More complex): first-pass metabolism reduces extent

A drug is orally administered. Gut wall/liver metabolism reduces F. Another drug of the same dose shows minimal first-pass effect.

• High first-pass effect → lower F → lower systemic AUC.

• Lower AUC can mean the effective concentration is reached later or not at all (depending on required exposure).

• Absorption rate might be similar, but onset can still differ due to reduced extent.

Now you try

Drug X has strong first-pass metabolism; Drug Y has weak first-pass metabolism. If both are absorbed at the same rate, which is more likely to have a lower AUC after oral dosing, and how can that affect onset?

__________________________________________________

__________________________________________________

__________________________________________________

__________________________________________________

Practice Questions

• (Easy) Define bioavailability (F) and state its value for IV dosing.

__________________________________________________

__________________________________________________

__________________________________________________

• (Easy) Give two reasons why oral dosing often has different onset compared with IV dosing.

__________________________________________________

__________________________________________________

__________________________________________________

__________________________________________________

• (Medium) Explain how first-pass metabolism affects absorption extent and what marker of exposure is likely to change (mention AUC).

__________________________________________________

__________________________________________________

__________________________________________________

__________________________________________________

• (Medium) A formulation changes the absorption rate but not the overall bioavailability. What happens to onset and AUC?

__________________________________________________

__________________________________________________

__________________________________________________

__________________________________________________

• (Hard) A drug shows delayed onset after oral administration, but the final plasma

concentration (AUC) is unchanged compared with a reference. Explain two possible causes and link each cause to onset.

__________________________________________________

__________________________________________________

__________________________________________________

__________________________________________________

• (Hard) Compare the effect of (i) reduced gastric emptying and (ii) higher intestinal permeability on onset and extent. State what changes in rate vs F/AUC for each.

__________________________________________________

__________________________________________________

__________________________________________________

__________________________________________________

Answer Key

• Bioavailability (F) is the fraction of the administered dose that reaches the systemic circulation; for IV dosing, F = 1 (100%).

• Examples: No absorption step for IV (immediate systemic availability); oral has absorption + possible first-pass metabolism (gut/liver reduce extent and can delay onset).

• First-pass metabolism reduces extent (lower F ), so AUC decreases; onset may be delayed because systemic concentrations rise less and may take longer to reach effective levels.

• If F is unchanged, AUC stays the same but onset changes: faster absorption → earlier onset; slower absorption → later onset.

• Possible causes: delayed gastric emptying or enteric coating delay the absorption rate (onset later) while total absorbed amount can remain similar (AUC unchanged). Another cause is rate-limiting absorption step that affects timing but not overall fraction absorbed.

• (i) Reduced gastric emptying slows delivery to small intestine → slower rate → later onset, extent may be similar (AUC often similar if absorption completes). (ii) Higher intestinal permeability increases absorption rate (and potentially F) → earlier onset; extent may increase (higher AUC) if permeability limits absorption previously.

Exam Tips & Common Mistakes

• Don’t mix up onset (rate/early rise) with extent (overall exposure measured by AUC).

• If the question mentions “same AUC”, don’t propose changes that alter F; instead focus on absorption rate (formulation, GI transit, dissolution).

• When you see oral vs IV, remember IV bypasses absorption and first-pass - so differences are mainly F and absorption rate.

• Avoid vague answers like “it absorbs better”; specify whether it changes rate (when Cmax/effective level is reached) or extent (AUC/F).

• Examiner phrasing: for 8-12 marks, use two linked causes (rate factor + extent/first-pass factor) and state the expected direction for onset and AUC.

Quick marker-focused phrases to include

• “This affects the absorption rate and therefore the onset

End of chapter one. 4 more chapters in the full book.