Effect of liver failure, renal failure, critical illness, ageing and pregnancy on pharmacokinetics, and the need for dose adjustment in these circumstances

Overview

Liver failure, renal failure, and critical illness each alter drug pharmacokinetics through distinct but sometimes overlapping mechanisms - reduced metabolic/excretory clearance, altered protein binding, and changed volume of distribution - requiring individualised dose adjustment beyond standard population dosing references, which are typically validated in stable, organ-function-normal populations
Relevant to essentially all prescribing in critically unwell or organ-impaired patients, a population where standard dosing references may not reliably apply

Liver failure reduces hepatic drug metabolism and also reduces synthesis of albumin (increasing free fraction of highly protein-bound drugs) - both mechanisms increasing effective drug exposure at a standard dose; renal failure reduces clearance of renally-eliminated drugs and their metabolites; critical illness combines fluctuating organ perfusion, capillary leak-related volume of distribution changes, and often reduced albumin, producing pharmacokinetic effects that are harder to predict from any single measured parameter than in either isolated organ failure alone

Standard creatinine-based renal function estimation formulas have specific limitations in critical illness (rapidly changing renal function, altered muscle mass) and should be interpreted cautiously rather than assumed reliably accurate in this population
Hepatic impairment lacks as standardised a dosing-adjustment framework as renal impairment (no equivalent to eGFR-based dosing tables for most drugs), often requiring clinical judgement and, where available, therapeutic drug monitoring

Dose reduction, interval extension, or drug avoidance guided by the specific organ impairment pattern and the individual drug's clearance dependence
Therapeutic drug monitoring, where available for the specific agent, is particularly valuable in this population given the reduced reliability of standard dosing predictions

Hypoalbuminaemia increasing free (active) fraction of highly protein-bound drugs in liver failure, critical illness pharmacokinetic unpredictability (see also ), augmented renal clearance in some critically ill patients

Hepatic impairment lacks the standardised, formula-based dosing adjustment framework that exists for renal impairment (no direct hepatic equivalent to eGFR-based dosing tables for most drugs) - dose adjustment in significant liver disease therefore relies more heavily on clinical judgement, drug-specific knowledge, and therapeutic drug monitoring where available, rather than a simple calculable adjustment

5 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.