Pharmacokinetics

Key ConceptsThis chapter covers how drug absorption and bioavailability control onset of effect (when plasma drug levels rise enough to produce pharmacological action). For exams, you need both the rate (how fast levels rise) and the extent (how much drug reaches systemic circulation).

Core ideas you must knowOnset depends on absorption rate + distribution + elimination

Faster absorption → earlier rise in plasma concentration → earlier onset (assuming target exposure is reached).

Bioavailability (F) determines the extent of exposure

If F is low, systemic exposure is low even if absorption is fast.

Route matters

IV: F = 1 (100% reaches systemic circulation immediately).

Oral: F < 1 due to incomplete absorption and first-pass metabolism.

Absorption rate is influenced by drug + formulation + physiology

Examples: gastric emptying, intestinal transit, solubility, permeability, surface area, food effects.

Absorption extent is influenced by first-pass effect and incomplete uptake

First-pass metabolism in gut wall/liver reduces F.

Concentration-time shape links to PK

Faster absorption often gives a steeper early rise in concentration-time curve.

Before you continueCan you explain, in one paragraph, why an oral dose can have a delayed or weaker onset compared with the same dose given IV?

Key TermsAbsorption - Movement of drug from the administration site into systemic circulation.

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 RecallAbsorption - __________

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Bioavailability (F) - __________

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First-pass metabolism - __________

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Absorption rate - __________

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Onset of action - __________

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AUC (Area Under the Curve) - __________

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Permeability - __________

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Worked ExamplesExample 1 (Straightforward): IV vs Oral onsetA 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.

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Example 2 (Rate vs extent): formulation changes absorption rateTwo 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.

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Example 3 (More complex): first-pass metabolism reduces extentA drug is orally administered....