Example: A hypothetical drug is completely metabolized (fm = 1) by the liver to a metabolite which is eliminated entirely by the kidney. A decrease in the liver function can result in slower rate of drug metabolism without affecting the renal excretion of the metabolite. Also, a decrease in kidney function can affect the rate of metabolite elimination without affecting the parent drug metabolism. Discuss the differences in drug and metabolite pharmacokinetics in patients with liver dysfunction and in patients with kidney dysfunction.
Reduced liver function decreases the drug clearance, and slows the rate of metabolite formation however the amount of metabolite formed will not change (100 % metabolism). The metabolite clearance does not change because it is eliminated by the kidney.
Reduced kidney function does not affect the clearance of the parent drug and the formation of the metabolite. However reduced kidney function decreases the metabolite clearance.
Patients with liver dysfunction
The reduced liver function reduces the drug clearance (and also the rate of metabolite formation), without affecting the amount of metabolite formed.
The metabolite clearance is not affected by the decrease in liver function since it is eliminated completely by the kidney.
Patients with kidney dysfunction
The reduced kidney function will not affect the drug clearance and will not affect the amount of metabolite formed (the drug is 100% metabolized).
The metabolite clearance will be lower due to the reduced kidney function since the metabolite is eliminated by the kidney and will result in larger metabolite AUC.
