Unit 5: Bioavailability, ADME, and Bioequivalence

What are the three core concepts in Unit 5?

ADME, Bioavailability, Bioequivalence.

Why are ADME, bioavailability, and bioequivalence important?

They determine how well a drug works, how quickly it acts, and whether products can be safely substituted.

What does ADME stand for?

Absorption, Distribution, Metabolism, Excretion.

What does ADME describe?

The journey of a drug through the body from administration to elimination.

What is absorption?

Movement of a drug from site of administration into the bloodstream.

Most oral drug absorption occurs where?

Small intestine (not stomach).

Factors affecting absorption?

Drug formulation, gastric pH, food, drug interactions.

Example of drug interaction reducing absorption?

Antacids reducing tetracycline absorption.

IV administration bioavailability?

100% (bypasses absorption).

Do topical drugs have high systemic absorption?

No, usually limited and act locally.

What is distribution?

Movement of drug from bloodstream into tissues and fluids.

Factors affecting distribution?

Blood flow, protein binding, lipid solubility.

Highly protein-bound drugs risk?

Drug displacement and toxicity.

Example of highly protein-bound drug?

Warfarin.

Lipid-soluble drugs tend to accumulate where?

Fatty tissue.

Water-soluble drugs remain where?

Bloodstream and extracellular fluid.

What is metabolism also called?

Biotransformation.

Primary organ of metabolism?

Liver.

Main enzyme system involved?

CYP450.

What is first-pass metabolism?

Liver metabolism before reaching systemic circulation.

What is a prodrug?

Drug requiring metabolic activation.

Example of prodrug?

Codeine → morphine.

CYP450 inhibitors effect?

Increase drug concentrations.

CYP450 inducers effect?

Decrease drug effectiveness.

Example CYP inhibitor?

Ketoconazole.

Example CYP inducer?

Rifampin, St. John’s Wort.

Primary route of excretion?

Kidneys (renal).

Other excretion routes?

Biliary, lungs.

What is enterohepatic recycling?

Drug reabsorbed from intestine prolonging effect.

Kidney impairment effect?

Drug accumulation and toxicity.

Define bioavailability.

Percentage of administered dose reaching systemic circulation in active form.

IV bioavailability?

100%.

Why is oral bioavailability lower?

Incomplete absorption + first-pass metabolism.

Routes partially bypassing first-pass?

Sublingual, transdermal, rectal.

Why is oral morphine dose higher than IV?

Extensive first-pass metabolism.

Bioavailability affects what?

Dosing.

Why must ER and IR not be interchanged?

Different absorption profiles.

Dosage form affects bioavailability how?

Immediate vs extended-release changes absorption rate.

Solubility effect?

Lipophilic drugs absorb more easily.

Food impact?

Can increase or decrease absorption.

Drug interaction example?

Calcium reduces tetracycline absorption.

Patient-specific factors?

age, disease state, liver function.

Define bioequivalence.

Two products deliver same amount of drug at same rate and extent.

Bioequivalence compares what?

Brand vs generic products.

FDA criteria for bioequivalence?

No significant difference in rate and extent of absorption.

Rate of absorption known as?

Cmax.

Extent of absorption known as?

AUC.

Does PTCB require Cmax/AUC memorization?

No, but understand rate and extent concepts.

Bioequivalence alone equals therapeutic equivalence?

No.

Requirements for therapeutic equivalence?

Pharmaceutical equivalence + bioequivalence + FDA standards.

Pharmaceutical equivalence means?

Same active ingredient, dosage form, and strength.

Orange Book purpose?

Lists therapeutic equivalence codes.

AB rating means?

Interchangeable.

BX rating means?

Not substitutable.

Why must digoxin be monitored?

Narrow therapeutic index; small bioavailability changes cause toxicity.

Why cautious with phenytoin generic switching?

Tight therapeutic margins.

Why is nitroglycerin not given orally?

First-pass metabolism.

Why must PPIs delayed-release be swallowed whole?

Protect bioavailability.

Why is levothyroxine not always interchangeable?

Small bioavailability differences destabilize thyroid levels.

Why is warfarin bioequivalence critical?

Over/under anticoagulation risk.

Why monitor cyclosporine brand vs generic?

Variability impacts transplant rejection risk.

Where does most oral absorption occur?
A. Stomach
B. Small intestine
C. Liver
D. Colon

B. Small intestine

Which route has 100% bioavailability?
A. Oral
B. Sublingual
C. IV
D. Rectal

C. IV

First-pass metabolism primarily occurs in the:
A. Kidneys
B. Lungs
C. Liver
D. Intestine

C. Liver

A CYP450 inhibitor will most likely:
A. Decrease drug levels
B. Increase drug levels
C. Prevent absorption
D. Increase excretion

B. Increase drug levels

AB rating in Orange Book means:
A. Not interchangeable
B. Brand only
C. Interchangeable
D. Experimental

C. Interchangeable

Which drug requires careful monitoring due to narrow therapeutic index?
A. Amoxicillin
B. Digoxin
C. Acetaminophen
D. Loratadine

B. Digoxin

A patient switches from immediate-release to extended-release without dose adjustment. What is the primary risk?
A. Faster onset
B. Reduced absorption variability
C. Altered bioavailability and toxicity
D. Increased excretion

C. Altered bioavailability and toxicity

A patient takes ciprofloxacin with antacids. What occurs?
A. Increased metabolism
B. Chelation reduces absorption
C. Increased protein binding
D. Faster excretion

B. Chelation reduces absorption

A highly protein-bound drug is added to warfarin therapy. What may happen?
A. Increased renal clearance
B. Displacement and bleeding risk
C. Decreased distribution
D. Reduced metabolism

B. Displacement and bleeding risk

A drug undergoes enterohepatic recycling. What is the clinical result?
A. Faster elimination
B. Reduced absorption
C. Prolonged drug effect
D. Increased renal toxicity

C. Prolonged drug effect

A generic product shows identical rate but lower extent of absorption compared to brand. Is it bioequivalent?
A. Yes
B. No

B. No