What drugs are CYP3A4 substrates?

What drugs are CYP3A4 substrates?

To date, the identified clinically important CYP3A4 inhibitors mainly include macrolide antibiotics (e.g., clarithromycin, and erythromycin), anti-HIV agents (e.g., ritonavir and delavirdine), antidepressants (e.g. fluoxetine and fluvoxamine), calcium channel blockers (e.g. verapamil and diltiazem), steroids and their …

What does CYP3A4 substrate mean?

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 drugs are strong 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 CYP2C8 substrates?

CYP2C8 substrate drugs include amodiaquine, cerivastatin, dasabuvir, enzalutamide, imatinib, loperamide, montelukast, paclitaxel, pioglitazone, repaglinide, and rosiglitazone, and the number is increasing. Similarly, many drugs have been identified as CYP2C8 inhibitors or inducers.

How many drugs are metabolized by CYP3A4?

CYP3A4 metabolizes more than 1900 drugs: 1033 act as substrates (897 major, 136 minor); 696, as inhibitors (118 weak, 437 moderate, and 141 strong); and 241, as inducers of the CYP3A4 enzyme [113].

What induces CYP3A4?

John’s wort extract or Hypericum perforatum L. is among the most commonly used herbal medications in the United States and clinical reports indicate that it induces the CYP3A4 enzyme and reduces plasma concentrations of substrate drugs (Roby et al. 2000; Komoroski et al. 2004). Interactions between warfarin and St.

What does CYP3A4 do in the body?

CYP3A4 is a major cytochrome P450. It catalyses a broad range of substrates including xenobiotics such as clinically used drugs and endogenous compounds bile acids. Its function to detoxify bile acids could be used for treating cholestasis, which is a condition characterised by accumulation of bile acids.

What does a drug substrate mean?

Definitions. substrates are drugs or other substances (xenobiotics) which are metabolized by cytochrome enzymes including 1. pharmacologically active drugs which require metabolism to inactive form for clearance from the body. metabolically activated drugs (prodrugs) which require conversion to active drug.

What are strong CYP3A 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 drugs are P gp substrates?

Examples of drugs that are substrates of P-gp efflux pump include: Apixaban, colchicine, cyclosporine, dabigatran, digoxin, edoxaban, rivaroxaban, and tacrolimus. The degree of effect on P-gp substrate serum concentration may be altered by dose and timing of orally administered P-gp inhibitor or inducer.

What are CYP3A4 inducers?

CYP3A4 inducers are drugs that increase the activity of CYP3A4. Note that the CYP3A4 enzyme is particularly susceptible to enzyme inducers, and marked reductions in the plasma concentrations of CYP3A4 substrates may occur.

What is a CYP450 substrate?

What is the CYP3A4 responsible for?

What is the role of CYP3A4?

What is the difference between CYP3A4 and CYP3A?

CYP3A4 is the most abundantly expressed CYP and accounts for approximately 30 to 40% of the total CYPcontent in human adult liver and small intestine. 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.

What are CYP3A inhibitors or inducers?

Is dexamethasone a CYP3A4 inducer?

Dexamethasone is a steroidal antiinflammatory agent which is used e.g. in the treatment of chronic inflammatory and autoimmune diseases. It is also effective as an antiem- etic agent in cancer chemotherapy. In cultures of human hepatocytes, dexamethasone is a potent inducer of CYP3A4 (Pichard et al. 1992).

What are CYP450 inducers and inhibitors?

The cytochrome P450 (CYP450) enzymes are essential to produce numerous agents, including cholesterol and steroids. They are also necessary for the detoxification of foreign chemicals and the metabolism of drugs. Drugs that cause CYP450 drug interactions are referred to as either inhibitors or inducers.

What drugs are substrates of cytochrome P450?

Significant Cytochrome P450 Enzymes and Their Inhibitors, Inducers, and Substrates

Is simvastatin a CYP3A4 substrate?

Simvastatin and atorvastatin, two widely prescribed cholesterol lowering medicines, are both metabolised by the isoenzyme cytochrome P450 3A4 (CYP3A4).

What are moderate CYP3A4 inhibitors?

Moderate inhibitors of CYP3A4 include: amiodarone, erythromycin, fluconazole, miconazole, diltiazem, verapamil, delavirdine, amprenavir, fosamprenavir, conivaptan.

Is dexamethasone a CYP3A4 substrate?

The CYP3A subfamily enzymes metabolize ~30% of clinically used drugs from almost all therapeutic categories [26]. Current evidence suggests that dexamethasone is a substrate for CYP3A4.

How do you remember P450 inducers and inhibitors?

Cytochrome P450 (CYP450) enzymes can be inhibited or induced by some drugs, resulting in significant drug interactions that can cause unanticipated adverse reactions or therapeutic failures. An easy way to remember the mnemonic is; CRAP GPs spend all day on SICKFACES.com.

What are CYP enzyme substrates?

Some Common Substrates, Inhibitors and Inducers of CYP450 Isoenzymes

Is warfarin a CYP3A4 substrate?

The anticoagulant drug warfarin occurs as a pair of enantiomers that are differentially metabolized by human cytochromes P450 (CYP). R-warfarin is metabolized primarily by CYP1A2 to 6- and 8-hydroxywarfarin, by CYP3A4 to 10-hydroxywarfarin, and by carbonyl reductases to diastereoisomeric alcohols.