Cytochrome P-450-Substrate Interaction and Hepatic Drug Metabolism in the Mouse

A drug which has entered the circulation, may be eliminated as such by the kidney and excreted in the urine. This depends on the lipid-solubility (lipophilicity) of the drug. In the kidney, lipid-soluble drugs are reabsorbed by the tubules, whereas water-soluble (hydrophilic) compounds cannot cross the tubular membrane. Upon passing through the liver some lipophilic drugs can be modified by conjugation with polar molecules, in order to be excreted in the bile or the urine, for example in the form of glucuronides. A large number of drugs, however, do not possess reactive groups for conjugation, They might tend to remain in the body, which is, in many cases, undesirable. In the liver, however, an enzyme system is present, which is capable of metabolizing these compounds by introducing polar groups with the aid of molecular oxygen, The metabolites produced may be excreted either directly or after subsequent conjugation,