Dose adjustment

Dose adjustment is the practice of modifying how much of a drug a person takes based on a characteristic of that person rather than on the therapeutic goal. The most common drivers are reduced kidney function, reduced liver function, or the presence of another drug competing for the same metabolic enzyme — all of which change how quickly the body clears a substance from circulation.

Published adjustment recommendations always attach to a measured value. For kidney function that is typically creatinine clearance or estimated glomerular filtration rate (eGFR); for liver function it may be a composite score such as Child-Pugh. This is why adjustments appear as threshold tables — reduce dose by X at clearance below Y — rather than a single figure. A person's clearance category, not the drug's intended effect, sets the number.

How it works · its role

Most drugs leave the body by one of two routes: the kidneys filter and excrete them in urine, or liver enzymes — particularly the CYP450 family — convert them into water-soluble metabolites that can be excreted. Standard doses are calibrated for typical clearance rates.

When either pathway is impaired, the drug lingers longer than expected. In someone whose kidneys or liver function below that baseline, the same dose can accumulate to concentrations intended for a faster-clearing body, raising toxicity risk without any change in what was taken.

The same logic applies when two substances compete for the same enzyme. If both are CYP2D6 substrates, each slows the other's clearance, effectively raising the active concentration of both. A dose calibrated for a person taking neither drug may be meaningfully too high for a person taking both. Age, body weight, and genetic variation in enzyme expression can also shift clearance, though kidney and liver function and drug interactions account for the largest and most predictable differences.

Relevance to substances & effects

Many psychoactive substances are substrates of the CYP enzyme system, meaning their effective level in the body can be raised or lowered by enzyme inhibitors or inducers taken alongside them. MAOIs suppress several metabolic pathways that other substances depend on — this is one of the mechanisms behind the severe interactions they carry.

Opioids, benzodiazepines, and many sedatives rely heavily on hepatic metabolism. In someone with significant liver impairment, these substances clear more slowly and accumulate at standard doses. Lithium sits at the other extreme: it is eliminated almost entirely by the kidneys, making renal clearance the single critical variable for safe use.

Because dose ranges on these pages are calibrated for people with typical clearance, readers with kidney or liver conditions — or who take enzyme-affecting medications — should treat the figures as a starting point for discussion with a clinician, not as directly applicable targets.