The liver is the primary site for drug biotransformation because it contains a high concentration of cytochrome P450 enzymes responsible for metabolizing drugs. These enzymes chemically modify substances to facilitate their elimination from the body. The liver's extensive blood supply from the portal vein allows it to efficiently process orally absorbed drugs before reaching systemic circulation. This first-pass metabolism significantly influences drug bioavailability and therapeutic effect. Other organs like the kidney, lung, and spleen play secondary roles in drug metabolism or elimination but do not possess the same enzymatic capacity as the liver.

Reference: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, Brunton et al., 13th Edition.