What is ADME?
ADME stands for Absorption, Distribution, Metabolism, and Excretion—essentially, the journey your medicine takes from the moment you take it until your body completely eliminates it. Think of it like a delivery system: the drug gets delivered (absorbed), transported to where it’s needed (distribution), modified so your body can get rid of it (metabolism), and finally removed (excretion).
Stage 1: Absorption (Drug Enters Body)
Drug moves from administration site into bloodstream. Key Points:Oral drugs absorbed in GI tract; takes time
First-pass metabolism: Liver breaks down oral drugs before they reach general circulation, reducing bioavailability.
Bioavailability (F): % of drug reaching bloodstream (IV = 100%, oral = 50-90%) Factors: Food, stomach pH, GI motility, drug chemistry
Stage 2: Distribution (Drug Spreads in Body)
Drug travels from blood to tissues and organs. Key Points:Volume of Distribution (Vd): How much of body the drug spreads into
Protein binding: Drugs stick to blood proteins (albumin); high binding = stays in blood longer Barriers: Blood-brain barrier blocks some drugs from reaching brain
Example: Warfarin 99% protein-bound → long half-life; Theophylline 40% bound → shorter half-life
Stage 3: Metabolism (Body Modifies Drug)
Liver transforms drug to make it eliminable.
Phase I: Cytochrome P450 (CYP) enzymes break apart or modify drug structure via oxidation, reduction, hydrolysis CYP3A4 handles ~75% of all drugs
Phase II: Conjugation adds water-soluble groups:Glucuronidation (morphine, acetaminophen)Sulfation (acetaminophen)Acetylation (isoniazid)Glutathione conjugation (detoxifies toxic metabolites) Factors affecting metabolism:Genetic polymorphisms (slow vs. fast metabolizers) Age, liver disease, concurrent drugs Enzyme inducers (rifampin, carbamazepine) speed metabolism
Enzyme inhibitors (ketoconazole, cimetidine) slow metabolism
Stage 4: Excretion (Drug Leaves Body)
Drug and metabolites removed via urine, bile, lungs.Key Points:Renal excretion (primary): Filtration, active secretion, reabsorption
Hepatic excretion: Larger metabolites eliminated in bile
Half-life (t₁/₂): Time for drug level to drop 50%Formula: t₁/₂ = 0.693 × (Vd / Clearance)Warfarin: 50 hours; Theophylline: 8 hours Kidney/liver disease → slower elimination → dose adjustment needed.
Why ADME Matters
Different routes, different doses: Oral needs higher dose due to first-pass metabolism.
Drug interactions: Drugs competing for metabolism or protein binding sites.
Kidney/liver disease: Must reduce doses; slower clearance.
Genetic differences: Some people are “fast” or “slow” metabolizers.
Elderly patients: Slower kidney/liver function = need lower doses.
Food/drug interactions: Grapefruit juice inhibits CYP3A4; charcoal grilling induces enzymes.
What your thoughts on ADME?