ABSTRACT
The segment-specific distribution of many drug metabolism enzymes sometimes makes it difficult to properly study or even detect certain reaction pathways. A suitable alternative to in vivo study of metabolism can be the use of a variety of in vitro models. The simplest in vitro model in terms of its preparation is that of the isolated perfused kidney. It has the advantage that extrarenal metabolism is eliminated. The major Phase I or oxidative metabolism enzymes in the kidneys exhibit similar biochemistry as those in the liver, although there are significant differences based on patterns of expression and nephron heterogeneity. Phase II metabolism reactions include the various conjugation reactions, such as glucuronidation, sulfation, and glutathione conjugation. Although acetaminophen is a widely used analgesic that is considered very safe to use under normal conditions, it can exhibit significant organ toxicity under overdose conditions. The kidneys possess most of the same drug metabolizing enzymes as the much more studied liver.
