PharmacologyTier 1Medical Sciences concept

Oral bioavailability calculation (AUC ratio method)

Core concept

F = fraction of an administered dose reaching the systemic circulation unchanged
IV is the reference standard: F(IV) = 1 by definition
AUC is the exposure integral, so comparing dose-normalised AUCs isolates absorption + first-pass loss

```

F = (AUC-oral / Dose-oral) / (AUC-IV / Dose-IV)

```

Same dose both routes simplifies to F = AUC-oral / AUC-IV
Two determinants, multiplied together
- f-abs - fraction absorbed across the gut wall (solubility, permeability, P-gp efflux, transit)
- 1 - E(H) - fraction surviving hepatic first pass
- F = f-abs x (1 - E(H))

Worked example: 100 mg PO gives AUC 300 mg.h/L; 50 mg IV gives AUC 300 mg.h/L
- F = (300/100) / (300/50) = 3/6 = 50%
AUC reflects clearance, not absorption alone - AUC = F x Dose / CL, so the calculation only holds if clearance is unchanged between the two study occasions
- Requires a crossover design or a stable-isotope IV tracer
Dose conversion: Dose-oral = Dose-IV / F

Drug	Approximate F	Reason
Furosemide	~50% (highly variable)	Erratic absorption; gut oedema in HF
Propranolol, morphine, GTN	20-40%	High hepatic extraction
Levothyroxine	~75%	Food, calcium, iron, PPI interference
Digoxin, phenytoin	>90%	Little first pass
Alendronate	~1%	Poor permeability

Bioavailability is not bioequivalence - bioequivalence requires the 90% CI of the AUC and Cmax ratio to fall within 80-125%
F does not predict onset or peak effect - Cmax and Tmax do

IV to oral furosemide conversion: roughly double the dose (40 mg IV to 80 mg PO)
- Decompensated HF with gut wall oedema absorbs even less - the reason IV works when oral has failed
Switching a high-extraction drug from IV to oral demands a large dose increase (propranolol, morphine, metoprolol)
Anything raising bioavailability raises exposure: P-gp or CYP3A4 inhibitors (grapefruit inc simvastatin AUC several-fold)
Vomiting, short bowel, bariatric surgery, gastroparesis and enteral feeds all cut F unpredictably - use IV where the endpoint matters
Rectal, sublingual, transdermal and inhaled routes bypass the portal circulation - GTN sublingual works where swallowed GTN does not

3 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.