Pharmacokinetics · Short notes

Absorption and Bioavailability: Short Notes & Cheat Sheet

Absorption mechanisms, the pH-partition theory, dissolution, first-pass metabolism, bioavailability calculations and the BCS.

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Short notes

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Where an oral dose is lost

Bioavailability is what survives every step. A drug can fail at dissolution, permeation or first-pass metabolism.

How drugs cross membranes

Passive diffusion (most drugs) moves lipid-soluble, unionised drug down its concentration gradient (Fick's law).
Carrier-mediated transport is saturable; active transport uses energy and can work against the gradient (levodopa uses an amino acid carrier).
Endocytosis handles large molecules (vitamin B12 with intrinsic factor). P-glycoprotein pumps some drugs back into the gut lumen.
pH-partition theory: weak acids are more unionised in acid and weak bases in alkali. Even so, most absorption happens in the small intestine because of its huge surface area.
Henderson–Hasselbalch: for acids, pH − pKa = log([A⁻]/[HA]); for bases, pH − pKa = log([B]/[BH⁺]).

What affects absorption

Dissolution often limits absorption of poorly soluble drugs. Noyes–Whitney: dissolution rate = DA(Cs − C)/h, so smaller particles (larger area) dissolve faster.
Salt form, polymorph and particle size change dissolution rate.
Food usually slows gastric emptying. It increases absorption of griseofulvin (fatty meal) but reduces that of tetracyclines, alendronate and levothyroxine.
First-pass metabolism in gut wall and liver lowers oral bioavailability (glyceryl trinitrate, lidocaine, propranolol, morphine, verapamil).

Bioavailability

Bioavailability (F) is the fraction of a dose that reaches the systemic circulation unchanged; IV is 100% by definition.
Absolute F = (AUC oral × dose IV) ÷ (AUC IV × dose oral). Relative bioavailability compares two non-IV products.
Cmax and Tmax reflect the rate of absorption; AUC reflects the extent.
Biopharmaceutics Classification System (BCS): class I high solubility, high permeability; II low solubility, high permeability; III high solubility, low permeability; IV low solubility, low permeability.
BCS class I (and often III) drugs may qualify for a biowaiver of in vivo bioequivalence studies.

Cheat sheet

High-yield facts in one place. Cover the right-hand column and test yourself.

BCS classes

Class	Solubility / permeability · examples
I	High / high · metoprolol, propranolol
II	Low / high · ibuprofen, carbamazepine, glibenclamide
III	High / low · atenolol, metformin, cimetidine
IV	Low / low · hydrochlorothiazide, furosemide

Parameter → meaning

Parameter	Reflects
Cmax	Peak concentration (rate and extent)
Tmax	Time to peak (rate)
AUC	Total exposure (extent)
F	Fraction reaching the circulation

Memory aids

BCS: 'Solubility falls in II, Permeability falls in III': Class I is best (both high), class II loses solubility, class III loses permeability, class IV loses both.

Exam traps

Weak acids are unionised in the stomach, yet most are still absorbed in the small intestine.
AUC reflects extent of absorption; Tmax reflects rate.
First-pass metabolism happens only for doses that pass through the liver before reaching the systemic circulation (oral route).
For BCS class II drugs, dissolution is the rate-limiting step.

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