What is the mechanism of action of etravirine?
Mechanism of Action Etravirine binds directly to reverse transcriptase and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme’s catalytic site. Etravirine does not inhibit the human DNA polymerases alpha, beta, and gamma.
Which drugs are NNRTIs?
Approved NNRTIs include delavirdine, efavirenz, etravirine, nevirapine, and rilpivirine (Fig. 6.2).
Is Emtricitabine a CYP3A4 inhibitor?
At concentrations up to 14-fold higher than those observed in vivo, emtricitabine did not inhibit in vitro drug metabolism mediated by any of the following human CYP 450 isoforms: CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.
Is efv a NNRTI?
The two NNRTIs most commonly used are NVP and EFV. However, NVP can cause liver damage and severe rash, both of which can be fatal. EFV may also cause a rash, impair mental function, and cause foetal malformations.
What is etravirine used for?
Etravirine is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children 2 years of age and older who no longer benefit from taking other HIV medications. Etravirine is in a class of medications called non-nucleoside reverse transcriptase inhibitors (NNRTIs).
How does an NNRTI work?
NNRTIs work by binding to the HIV enzyme called reverse transcriptase, which is essential to the viral replication process, and therefore blocking HIV from making copies of itself. Dapivirine is an example of an NNRTI. NRTIs work by mimicking nucleotides that are the building blocks of viral DNA.
What is Nnrti?
The non-nucleoside reverse transcriptase inhibitors (NNRTIs) directly inhibit the HIV-1 reverse transcriptase (RT) by binding in a reversible and non-competitive manner to the enzyme. The currently available NNRTIs are nevirapine, delavirdine, and efavirenz; other compounds are under evaluation.
Is tenofovir a CYP3A4 inhibitor?
At concentrations substantially higher (~300-fold) than those observed in vivo, tenofovir did not inhibit in vitro drug metabolism mediated by any of the following human CYP450 isoforms: CYP3A4, CYP2D6, CYP2C9 or CYP2E1.
What is M184V?
“M184V” is the shorthand for methionine replacing valine at position 184 in reverse transcriptase. It is by far the most commonly encountered nucleoside reverse transcriptase inhibitor (NRTI) mutation after failure with regimens containing lamivudine (3TC) or emtricitabine (FTC).
Is etravirine a 2C9 substrate?
Etravirine (ETR) is a CYP3A4, 2C19, and 2C9 substrate and also undergoes glucuronidation in vitro. Unlike efavirenz and nevirapine, etravirine does not induce its own metabolism. ETR is a mild inducer of CYP3A4, 2B6, and glucuronidation in vitro, but also inhibits 2C9 and 2C19.
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.
What are the drug-drug interactions of etravirine?
As with other NNRTIs, etravirine has a relatively long half-life (41 ± 20 hours). As a substrate and inducer of CYP3A4 and an inhibitor of other cytochrome P-450 isozymes, etravirine has important drug-drug interactions. The drug cannot be co-administered with tipranavir, fosamprenavir, or atazanavir.
Is velpatasvir a CYP3A4 substrate?
Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.