What are CYP3A4 inhibitors?
Potent inhibitors of CYP3A4 include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit. Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, St. John’s Wort and glucocorticoids.
What are CYP3A inhibitors or inducers?
CYP3A inducers include the glucocorticoids, rifampin, carbamazepine, phenobarbital, and phenytoin. Among the many significant CYP3A inhibitors are grapefruit juice, erythromycin, ketoconazole, clarithromycin, and verapamil.
What foods are CYP3A4 inhibitors?
The inhibition of CYP3A4 by grapefruit juice is probably the most well-known example of food-drug inhibition [76, 163]. It was suggested that the flavanone naringin, the predominant flavanone in grapefruit, might be responsible for the observed interaction effect [164].
What does CYP3A4 substrate mean?
Drugs metabolized by CYP3A4 are called CYP3A4 substrates. Keep in mind that many drugs are metabolized by more than one CYP450 enzyme, and CYP3A4 may represent only one pathway.
Does amiodarone inhibit CYP3A4?
Amiodarone is a substrate of CYP3A4 and CYP2C8 and an inhibitor of CYP2C9, CYP2D6, CYP3A4, and p-glycoprotein.
What is the difference between CYP3A4 and CYP3A?
CYP3A5 is 83% homologous to CYP3A4, is expressed at a much lower level than CYP3A4 in the liver, but is the main CYP3A isoform in the kidney. CYP3A7 is the major CYP isoform detected in human embryonic, fetal and newborn liver, but is also detected in adult liver, although at a much lower level than CYP3A4.
How do you increase CYP3A4?
St. John’s wort and common valerian were the strongest inducing herbs. In addition to induction of CYP3A4 by St. John’s wort, common valerian and Ginkgo biloba increased the activity of CYP3A4 and 2D6 and CYP1A2 and 2D6, respectively.
Is amiodarone a strong CYP3A4 inhibitor?
Common Medications Classified as Weak, Moderate and Strong Inhibitors of CYP3A4. Summary: Moderate inhibitors of CYP3A4 include: amiodarone, erythromycin, fluconazole, miconazole, diltiazem, verapamil, delavirdine, amprenavir, fosamprenavir, conivaptan.
What does it mean if a drug is metabolized by CYP3A4?
Cytochrome P450 3A4 (abbreviated CYP3A4) (EC 1.14. 13.97) is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body.
What enzymes metabolize amiodarone?
In humans, cytochrome P450 3A (CYP3A4) is a major enzyme involved in the metabolism of amiodarone (AM) to its major metabolite, desethylamiodarone (DEA).
What is the potency of a CYP3A4 inhibitor?
Inhibitors of CYP3A4 can be classified by their potency, such as: Strong inhibitor being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.
How is conivaptan classified as a CYP3A inhibitor?
Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain preparation was used (e.g., high dose, double strength) or as a “moderate CYP3A inhibitor” when another preparation was used (e.g., low dose, single strength). (l) The classification is based on studies conducted with intravenously administered conivaptan.
How many substrates should be used for in vitro CYP3A4/5 inhibition?
* Recommend the use of 2 structurally unrelated CYP3A4/5 substrates for evaluation of in vitro CYP3A4/5 inhibition. Table 1-2: Examples of in vitro selective inhibitors for P450-mediated metabolism (9/26/2016) Most chemical inhibitors are not specific for an individual CYP enzyme.
Do P-gp inhibitors also inhibit CYP3A?
(a) Most of P-gp inhibitors also inhibit CYP3A. (b)In vivo data suggested specific inhibition of OAT1. AUC: area under the plasma concentration-time curve.