Expansion
Filtration of free drug, active secretion, and passive reabsorption depending on pH
Expansion
Three processes:
- Glomerular filtration: only the unbound fraction; highly protein-bound drugs such as warfarin are filtered poorly
- Active tubular secretion: through the organic anion and cation transporters; can clear protein-bound drug, and is saturable
- Passive reabsorption: only lipid-soluble, un-ionised drug crosses back, and this depends on urinary pH
Ion trapping is the exploitable principle: a drug that is ionised in the urine cannot diffuse back and is trapped.
- Weak acids (aspirin, phenobarbital, methotrexate) are ionised in alkaline urine, so urinary alkalinisation with bicarbonate increases their excretion
- Weak bases (amfetamine, quinine) are ionised in acidic urine
Practical implications in renal impairment: drugs cleared renally need dose reduction (digoxin, aminoglycosides, lithium, metformin, low molecular weight heparin), and some become ineffective or dangerous entirely.
Note that loop diuretics must reach the tubular lumen by secretion to work, so in renal impairment and hypoalbuminaemia higher doses are required.