Phase I and phase II

Phase I and phase II

The activity of metabolic enzyme systems have two classifications:

Phase I: in which oxidation, reduction, and hydrolysis reactions often breakdown the drug into a more reactive group which is both lower in lipid solubility (and thus can be renally excreted) and capable of undergoing phase II reactions.

Phase 2: conjugation reactions often result in inactive products which are even less lipid soluble and thus able to be excreted renally.

Although these reactions often happen sequentially

(Phase I leading to Phase II), it is possible for drugs just to be metabolised by Phase I or Phase II. An interesting example occurs with paracetamol. Normally paracetamol is metabolised by only two Phase II reactions. However, in situations of overdose, the glucuronidation reaction is overwhelmed and an alternative Phase I pathway is activated. Unfortunately, the Phase I reaction leads to the formation of a toxic metabolite which if produced in high enough amounts can lead to liver failure.