Reverse transcriptase inhibitors delavirdine

Nonnucleoside reverse transcriptase inhibitors Delavirdine should not be used with any rifamycin. Doses of nevirapine... 

Pharmacology Delavirdine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. Delavirdine binds directly to reverse transcriptase (RT) and blocks RNA-dependent and DNA-dependent DMA polymerase activities. 

Delavirdine mesylate is a member of the /7w(heteroaryl)piperazine (BHAP) class of nonnucleoside HIV-1 reverse transcriptase inhibitors (Adams et al., 1998 Romero et al., 1993 Romero, 1994). This class of compounds was discovered by Upjohn scientists from a computer-directed dissimilarity analysis of the Pharmacia Upjohn chemical library to select compounds for screening against HIV-1 RT. The result of the in vitro assay (Deibel et al., 1990) is an IC50 of 0.260 p,M, which is comparable to AZT. In accordance with the previous NNRTIs, delavirdine is a noncompetitive inhibitor of reverse transcriptase, and has a synergistic effect with nucleoside transcriptase and protease inhibitors (Chong et al., 1994). 

Many of the drugs likely to be taken by patients with HIV have a strong potential to interact with the protease inhibitors. In particular, the non-nucleoside reverse transcriptase inhibitors are also metabolised by CYP450 and have been shown to interact with protease inhibitors. Delavirdine is an inhibitor of CYP3A4 but nevirapine and efavirenz are inducers of CYP3A4. The protease inhibitors also interact with each other, and these interactions are being explored for their potential therapeutic benefits. 

Three non-nucleoside reverse transcriptase inhibitors (NNRTI) are currently used efavirenz (EFV), nevirapine (NVP) and delavirdine (DLV). The last NNRTI is not registered in Europe. 

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) delavirdine mesylate efavirenz nevirapine... 

Delavirdine is a synthetic nonnucleoside reverse transcriptase inhibitor which after directly binding to HIV-1 reverse transcriptase blocks RNA-dependent and DNA-dependent DNA polymerase activities. It disrupts the catalytic activity of the enzyme after causing a conformational change in HIV-1 reverse transcriptase and does not... 

More recently, RTIs that are chemically distinct from zidovudine and other NRTIs have also been developed (see Table 34-3). These agents are known as nonnucleoside reverse transcriptase inhibitors (NNR-TIs), and include drugs such as delavirdine (Rescrip-tor), efavirenz (Sustiva), and nevirapine (Viramune).32 These drugs also inhibit the reverse transcriptase enzyme, but act at a different site on the enzyme than do their NRTI counterparts. 

At the present time, there are at least 14 compounds that have been formally approved for the treatment of human immunodeficiency virus (HIV) infections. There are six nucleoside reverse transcriptase inhibitors (NRTIs) that, after their intracellular conversion to the 5 -triphosphate form, are able to interfere as competitive inhibitors of the normal substrates (dNTPs). These are zidovudine (AZT), didanosine (ddl), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir (ABC). There are three nonnucleoside reverse transcriptase inhibitors (NNRTIs) — nevirapine, delavirdine, and efavirenz — that, as such, directly interact with the reverse transcriptase at a nonsubstrate binding, allosteric site. There are five HIV protease inhibitors (Pis saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir) that block the cleavage of precursor to mature HIV proteins, thus impairing the infectivity of the virus particles produced in the presence of these inhibitors. 

Voorman RL, Maio SM, Hauer MJ, et al. Metabolism of delavirdine, a human immunodeficiency vims type-1 reverse transcriptase inhibitor, by microsomal cytochrome P450 in humans, rats, and other species probable involvement of CYP2D6 and CYP3A. Dmg Metab Dispos 1998 26(7) 63 l 639. 

The advent of highly active antiretroviral therapy (HAART) to minimize the rapid development of viral resistance in the treatment of HIV infection may result in multiple drug interactions (110-113). Both the nonnucleoside reverse transcriptase inhibitors and the protease inhibitors are substrates and inhibitors of some CYP enzymes, and some act as inducers as well (110,111). The major effects are on the CYP3A isoforms, and this has been used to advantage to increase concentrations of some HIV drugs. For example, delavirdine is a mechanism-based irreversible inhibitor of CYP3A4, and thereby is used to increase exposure to protease inhibitors (114). Ritonavir is a protease inhibitor, but it is used primarily for its ability as a potent inhibitor of CYP3A4 to increase concentrations of other protease inhibitors (115). 

Delavirdine is a non-nucleoside reverse transcriptase inhibitor, which is dosed three times daily. No food restrictions apply. It is metabolized mainly by CYP3A, and so interactions with other drugs that use this metabolic pathway can occur. 

In a review of the medical records of HIV-positive patients who had taken nevirapine, delavirdine, or both, the frequency of skin reactions was determined, as were the consequences of rechallenge with the same or the alternative agent (17). The overall incidence of rash attributed to the use of one of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 37%. While rash due to delavirdine was more common (8/20 versus 25/69), the rash due to nevirapine was more severe and necessitated more frequent hospitalization. Rash recurred in six of eight patients who were rechallenged with the same agent and in seven of 10 who were switched to the alternative agent. The conclusion was drawn that there is little value in attempting to re-treat patients who have had skin reactions to NNRTIs, except possibly those with limited treatment options. 

The non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs) include delavirdine, efavirenz, and nevirapine (all rINNs). The pharmaceutical chemistry and uses of the first- and second-generation NNRTIs have been reviewed (1). 

Successful treatment of human immunodeficiency virus (HIV-1) infection has been achieved through successful implementation of highly active antiretroviral therapy, frequently referred to as HAART. This involves simultaneous administration of both nucleoside and nonnucleoside reverse transcriptase inhibitors and one or more protease inliibitors. The common nucleoside reverse transcriptase inhibitors are the thymidine analogs didanosine (ddl), lamivudine (3TC), and zalcitabine (ddC) and the non-thymidine analogs abacavir (Ziazen), stavudine (d4T), and zidovudine (AZT). The nonnucleoside reverse transcriptase inhibitors include delavirdine, efavirenz, and nevirapine. The protease inhibitors include indinavir, nelfinavir, ritonavir, and saquinavir. Response to therapy is monitored by quantification of HIV-RNA copies (viral load) and CD-4+ T-lymphocyte count. Successful therapy is indicated when viral load is reduced to <50 copies/mL and CD-4+ count >500 per mL. 

A. Reverse transcriptase inhibitors, nevirapine, efavirenz, and delavirdine... 

Nonnucleoside RTIs that do not require metabolic activation (e.g., delavirdine and nevirapine, efavirenz, which are not myelosuppressants) and a nucleotide reverse-transcriptase inhibitor (adefovir) have been introduced. Resistance emerges rapidly if these drugs are used as individual agents for management of HIV infection. However, they may provide additive or synergistic activity against HIV if used in combination regimens with NRTIs and/or Pis. 

Delavirdine is an antiretroviral/nonnucleoside reverse transcriptase inhibitor that inhibits replication of HlV-1 infection by interfering with DNA synthesis. Delavirdine is indicated in treatment of HfV-l infection in combination with appropriate antiretroviral agents when therapy is warranted. 

Nonnucieoside reverse transcriptase inhibitors Nevirapine Delavirdine, efavirenz... 

Normucleoside reverse transcriptase inhibitor (NNRTI) used in combination regimens for HIV. Tox skin rash, CNS effects. Other NNRTIs delavirdine, nevirapine. 

Non-Nucleoside Reverse Transcriptase Inhibitor as Drugs for the Treatment of HIV Efavirenz, Nevirapine, Delavirdine, Apricitabine and Etravirine... 

Delavirdine, a nonnucleoside reverse transcriptase inhibitor, is used as part of antiretroviral therapy. Because of its moderate efficacy and inconvenient dosing (three times a day) as well as interaction with other protease inhibitors, delavirdine is currently rarely used (see footnote 1). 

Non-nucleoside reverse transcriptase Inhibitors (NNRTt) Delavirdine 5.8 h (range 2-11) Chronic Hepatotoxicity, rash. Hepatotoxicity, rash. ... 

Furthermore, delavirdine (Rescriptor) is a novel HIV-1 reverse transcriptase inhibitor for HIV-positive individuals and zafirlukast (Accolate) is an antiasthma drug. 

Furthermore, delavirdine (Rescriptor) is a novel HIV-1 reverse transcriptase inhibitor for HIV-positive individuals and zafirlukast (Accolate) is an anti-asthma drug. The anti-emetics ramosetron (Nasea) and dolasetron (Anzemet) are potent and highly selective 5-HTj receptor antagonists for die treatment of chemotherapy-induced nausea and vomiting. 

Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zalcitabine (production discontinued), and Zidovudine. Non-nucleoside Reverse Transcriptase Inhibitors include Delavirdine, Efavirenz, and Nevirapine. 

Rezk, N.L. TidweU, R.R. Kashuba, A.D.M. Simple and rapid quantification of the non-nucleoside reverse transcriptase inhibitors nevirapine, delavirdine, and efavirenz in human blood plasma using high-performance liquid chromatography with ultraviolet absorbance detection, J.Chromatogr.B, 2002, 774, 79-88. [SPE]... 

Stormer, E. von Moltke, L.L. Perloff, M.D. Greenblatt, D J. Differential modulation of P-glycoprotein expression and activity by non-nucleoside HlV-1 reverse transcriptase inhibitors in cell culture, Pharm.Res., 2002,19,1038 1045. [verapamil efavirenz nevirapine delavirdine]... 

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