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Cytochrome 450: Ultrarapid Metabolism

Pharmacokinetics is the study of how a drug is affected by the body (i.e. Absorption, distribution, metabolism, and excretion). Differences in genetic make-up alter a patient’s ability to respond to or metabolize a drug. Cytochrome P450 enzymes’ activities are governed by genetic polymorphisms resulting in phenotypes with varying abilities to perform their metabolic roles including reduced, normal, and increased metabolic activity. The highest end of the spectrum is the ultrarapid metabolizer group. Below are some examples of how ultrarapid metabolizers of a given enzyme will affect the pharmacokinetics of several drugs important to the practice of anesthesiology.

CYP2D6 converts codeine, tramadol, oxycodone, and hydrocodone to their active metabolites. Therefore, a patient who is an ultrarapid metabolizer of CYP2D6 will have an increased risk of side effects and toxicity (i.e. somnolence and respiratory depression).

CYP3A4 metabolizes alfentanil, fentanyl, midazolam, methadone, and sufentanil to their inactive metabolites. Therefore, a patient who is an ultrarapid metabolizer of CYP3A4 will require an increased dose, more frequent dosing, or may not be able to achieve therapeutic serum levels safely depending how rapid their enzymes metabolize the specific drugs.


  1. Belle DJ, Singh H. Genetic factors in drug metabolism. American family physician. 2008; 77(11), 1553-1560. PubMed Link

Other References

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed March 30, 2020. Link