With failure of the liver or kidneys, the excretion of some drugs may be impaired, leading to increased serum concentrations.

Renal failure

There are three approaches to dose adjustment in renal failure. The choice of approach depends on the drug selected (see table below):

1. Double the dosing interval (or halve the dosage in patients with severe renal insufficiency). Use for drugs that are relatively non-toxic.
2. Increase dosing interval 2-fold when creatinine clearance (Ccr) is 0.5–1.0 ml/min/kg, 3-fold when Ccr is 0.3–0.5 ml/min/kg and 4-fold when Ccr is <0.3 ml/min/kg.
3. Precise dose modification is required for some toxic drugs that are excreted solely by glomerular filtration (e.g. aminoglycosides). This is determined by using the dose fraction Kf to amend the drug dose or dosing interval according to the following equations:
   • Modified dose reduction = normal dose × Kf
   • Modified dose interval = normal dose interval/Kf
   • where Kf = patient Ccr/normal Ccr.

Where Ccr is unavailable, Ccr may be estimated at 88.4/serum creatinine (μmol (micromoles)/l) (where serum creatinine is <350 μmol/l). Kf may be estimated at 0.33 if urine is isosthenuric or 0.25 if the patient is azotaemic.

Hepatic insufficiency

Drug clearance by the liver is affected by many factors and thus it is not possible to apply a simple formula to drug dosing. The table below is adapted from information in the human literature.