Principles of pharmacology and pharmacokinetics - excretion

Definition

Drug excretion (elimination from the body, predominantly renal, with biliary/faecal and other minor routes for some drugs) determines a drug's half-life and, for renally-cleared drugs, requires dose adjustment in renal impairment - excretion is the final pharmacokinetic step following absorption, distribution, and metabolism
Relevant to dosing consideration for any drug with significant renal (or, less commonly, biliary) elimination, particularly important given the high prevalence of renal impairment in hospitalised and older patient populations

Renal excretion combines glomerular filtration, active tubular secretion, and tubular reabsorption - for predominantly renally-cleared drugs, reduced glomerular filtration rate directly reduces clearance, prolonging half-life and risking drug accumulation/toxicity if dosing is not adjusted accordingly
Enterohepatic recirculation (some drugs excreted in bile are reabsorbed from the intestine back into circulation) can prolong a drug's effective half-life beyond what renal excretion alone would predict

Renal function (estimated GFR/creatinine clearance) should be assessed before dosing any predominantly renally-cleared drug, with dose or interval adjustment per established references
Drug/metabolite accumulation risk in renal impairment is relevant not just to the parent drug but sometimes to active or toxic metabolites that are also renally cleared (e.g. morphine's active metabolites accumulating in renal impairment)

Dose or dosing interval reduction for renally-cleared drugs in renal impairment, avoiding or using with particular caution drugs with active renally-cleared metabolites in significant renal impairment (e.g. morphine, in favour of an opioid with less renally-dependent active metabolite accumulation)
Dialysis-relevant dosing considerations (some drugs are cleared by dialysis and require supplemental dosing after a session, others are not significantly dialysed)

Morphine active metabolite accumulation in renal impairment (a frequently tested example, favouring alternative opioids like fentanyl in significant renal impairment), enterohepatic recirculation prolonging effective half-life, dialysability of drugs in overdose (see )
Morphine's active metabolites (particularly morphine-6-glucuronide) are renally cleared and can accumulate in renal impairment, causing prolonged and potentially excessive opioid effect even with standard morphine dosing - this is a specific, frequently tested reason to prefer an opioid with less renally-dependent active metabolite handling (such as fentanyl) in patients with significant renal impairment

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