Expansion
ADME: Absorption, Distribution, Metabolism, Excretion
Expansion
ADME
- Absorption: bioavailability, affected by route, formulation, gut function and first pass metabolism
- Distribution: volume of distribution relates dose to plasma concentration. A large volume implies extensive tissue binding (digoxin, amiodarone), so haemodialysis is ineffective
- Metabolism: phase I (oxidation, mainly cytochrome P450) and phase II (conjugation), chiefly hepatic
- Excretion: renal for polar drugs, biliary for large ones
Key relationships
- Half-life = 0.693 x volume of distribution / clearance
- Steady state is reached after about 5 half-lives, and elimination likewise takes 5
- A loading dose depends on volume of distribution; a maintenance dose depends on clearance
Zero versus first order: most drugs show first order kinetics, with a constant proportion eliminated per unit time. Zero order drugs (phenytoin, alcohol, high dose aspirin) have saturated enzymes and eliminate a constant amount, so small dose increases cause disproportionate rises in concentration.
Therapeutic drug monitoring is needed for drugs with a narrow index: digoxin, lithium, aminoglycosides, phenytoin, vancomycin, ciclosporin.