Question

List the 3 most important CYP450 in drug metabolism in order

Answer 1

The most important CYP450 enzymes in drug metabolism are CYP3A4, CYP2D6, and CYP2C19, with CYP3A4 being the most prevalent. These enzymes are crucial in drug development due to their significant impact on the metabolism, efficacy, and safety of drugs across different populations.

Step-by-step explanation:

The three most important CYP450 enzymes in drug metabolism, in order of importance, are:

1. CYP3A4
2. CYP2D6
3. CYP2C19

These CYP isoforms play a crucial role in the hepatic clearance of many drugs and tend to exhibit high levels of polymorphism among different populations, which can have significant implications for both efficacy and toxicity. Therefore, understanding the relative contribution of each CYP isoform to the metabolism of a drug is vital. This includes conducting in vitro assays to determine CYP specificity, and assessment with specific inhibitors.

Due to the polymorphic nature of CYP2D6 and CYP2C19, drugs metabolized by these isoforms may have varying levels of effectiveness in different individuals. Non-CYP mediated pathways are often preferable for pro-drug conversion to minimize these liabilities in populations with high polymorphic expression.