Drug enhancers

The body employs a number of processes to biotransform foreign compounds like poisons, environmental pollutants and drugs. The cytochrome P450 (CYP) enzyme family is an important group of proteins known to catalyze the biotransformation of many drugs.

In some cases biotransformation results in a more active metabolite. In other cases biotransformation produces a less active metabolite that is more easily excreted from the body. If CYP enzymes are inactivated, drugs and foreign substances can accumulate to toxic levels.

An improved understanding of CYP mechanism of action has enabled the utilization of drug enhancers that induce or inhibit CYP activity. CYP metabolism can be increased by inducing gene synthesis of additional CYP proteins. CYP activity can be inhibited by reversibly or irreversibly blocking the binding site of the CYP enzyme. Many dangerous drug interactions come about as a result of unintended inhibition or induction of the CYP mechanism.

In the case of a drug that is metabolized by CYP3A4, such as the HIV integrase elvitegravir, the bioactivity and plasma concentration may increase if CYP3A4 is inhibited. Two drugs, FDA approved to enhance and extend the plasma concentration of HIV antiretrovirals metabolized by CYP3A4 include:

• Cobicistat is not active against HIV but when given with an HIV antiretroviral drug that is metabolized by CYP3A4 it can boost the plasma concentration and extend the activity of the drug by inhibiting hydrolysis of the drug by CYP3A4.
  • Cobicistat side effects are specific for CYP3A4 enzyme.
  • Cobicistat is approved to be formulated with either elvitegravir, tenofovir or emtricitabine as once a day tablet.
  • Cobicistat may be prescribed to be taken along with the protease inhibitors atazanavir or darunavir.
• Norvir (ritonavir) is a protease inhibitor primarily used to boost blood levels of other HIV medications in the body.
  • "ritonavir is a potent inhibitor of CYP3A. In vivo, ritonavir significantly increases the AUC of drugs primarily eliminated by CYP3A metabolism (e.g. clarithromycin, ketoconazole, rifabutin, and other HIV protease inhibitors, including indinavir, saquinavir and nelfinavir) with effects ranging from an increase of 77% to 20-fold in humans. It also inhibits CYP2D6-mediated metabolism, but to a significantly lesser extent (145% increase in desipramine AUC)".•

Many naturally occurring substances can inhibit or induce cytochrome P450. Nursing is often well positioned to educate the patient about the risk of drug interactions that can result from inhibitors and inducers of CYP metabolism. Patients must understand the importance of notifying their health providers of all nutrient supplements that they take, including herbal products. Many common plant substances have the potential to effect CYP activity but some present a significant danger of drug interaction including: Saint-John's wort, grapefruit, and golden seal.

©RnCeus.com