NAV

Cytochrome P-450 Interactions

Synonyms:

  • CYP450 Interaction Guidelines
  • Cytochrome P-450 Interaction Guidelines
According to Ogu CC, et. al. 1:

Cytochrome P450 is a family of isozymes responsible for the biotransformation of several drugs. Drug metabolism via the cytochrome P450 system has emerged as an important determinant in the occurrence of several drug interactions that can result in drug toxicities, reduced pharmacological effect, and adverse drug reactions.

The CYP 450 family of isozymes is responsible for approximately 75% of total drug metabolism 2. When curating these interactions in DrugBank, the following guidelines are used when determining the strength of a binding relationship between drugs and enzymes in the Cytochrome P450 family:

Substrate sensitivity:

Strong: >5 fold change in AUC for index sensitive substrate
Moderate: 2 - 5 fold
Not sensitive: < 2 fold

Inhibitor strength:

Strong: >5 fold change in AUC for index sensitive substrate
Moderate: 2 - 5 fold
Weak: 1.25 - 2 fold
Insignificant: <1.25

Induction strength:

Strong: >80% reduction in AUC for index sensitive substrate
Moderate: 50-80% reduction
Weak: 20-50% reduction
Insignificant: <20%

References:

  1. Ogu CC, Maxa JL: Drug interactions due to cytochrome P450. Proc (Bayl Univ Med Cent). 2000 Oct;13(4):421-3. [Article]
  2. Guengerich FP: Cytochrome p450 and chemical toxicology. Chem Res Toxicol. 2008 Jan;21(1):70-83. doi: 10.1021/tx700079z. Epub 2007 Dec 6. [Article]