Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) which shows good inhibitory activity against HIV-1. Reduced susceptibility to efavirenz has been reported with HIV-1 variants containing single and multiple mutations to the reverse transcriptase enzyme. In vitro and in vivo data suggest that the resistance profile of efavirenz overlaps with that of the NNRTIs nevirapine and delavirdine. Clinically significant drug interactions have been reported with efavirenz and indinavir and saquinavir. An increase in dosage of indinavir from 800 to 1000 mg 3 times daily is recommended during coadministration with efavirenz. Use of efavirenz in combination with saquinavir as the sole protease inhibitor is not recommended. Once-daily efavirenz in combination with zidovudine plus lamivudine or indinavir or nelfinavir increased CD4+ cell counts and reduced HIV RNA plasma levels to below quantifiable levels (< 400 copies/ml) in HIV-infected patients. A sustained reduction in viral load was maintained for at least 72 weeks in 1 study. Nervous system symptoms (including headache, dizziness, insomnia and fatigue) and dermatological effects (including maculopapular rash) appear to be the most common adverse events reported with efavirenz-containing antiretroviral regimens.
...
PMID:Efavirenz. 987 93

About one third of patients with HIV infection show neurological complications with considerable morbidity and high mortality. This is an actualized review of the most important neurological manifestations resulting from primary HIV infection, from secondary opportunistic infections, or as complications of antiretroviral therapy. The primary neurological manifestations, including HIV-associated dementia complex, myelopathies, peripheral neuropathies and myopathies, the more common opportunistic infections, primary central nervous system lymphoma and cerebrovascular diseases, are discussed in the light of new evidence in diagnosis, therapy and prognosis. Cognitive and psychiatric symptoms, visual changes, headache, seizures, dizziness, involuntary movements, gait disturbances, cranial neuropathies and focal deficits are the common neurological symptoms in HIV infection which are described under the aspect of differential diagnosis. It is important to bear in mind that nearly all information available to date on this subject concerns HIV patients in the period before combination therapies (including protease inhibitors). The introduction of highly active antiretroviral therapy (HAART) with protease inhibitors in 1995, and non-nucleoside reverse transcriptase inhibitors, have opened up new therapeutic modalities with a new emphasis on earlier detection and treatment of neurological complications. The prognosis of different HIV-associated neurological diseases has considerably improved, as recently shown in the case, for example, of progressive multifocal leucoencephalopathy.
...
PMID:[Neurological complications of HIV infection. Review: new diagnostic, therapeutic and prognostic aspects]. 1081 41

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. NNRTIs are extensively metabolized in the liver through cytochrome P450, leading to pharmacokinetic interactions with compounds utilizing the same metabolic pathway, particularly PIs, whose plasma levels are altered in the presence of NNRTIs. NNRTIs are drugs with a low genetic barrier, i.e. a single mutation in RT genoma induces a high-level of phenotypic resistance, preventing the use of NNRTIs as monotherapy. In naive patients, several trials have shown the value of NNRTIs in combination with nucleosides and/or protease inhibitors. Small pilot studies have shown that NNRTIs may be useful as second-line therapy. However, due to the rapid emergence of resistant virus to these compounds in case of incomplete viral suppression, NNRTIs should not be added to current failing antiretroviral regimen. The most common side-effect reported with nevirapine and delavirdine is rash. The incidence of rash is rather similar under these two compounds, but severe rash is less frequent with delavirdine. The most common adverse reactions reported with efavirenz are central nervous system complaints such as dizziness. Rash is reported less frequently than with nevirapine or delavirdine, and is usually mild. NNRTIs resistance mutations are located in the amino acid residues aligning the NNRTI-binding "pocket" site. High-level resistance is often associated with a single point mutation which develops within this site (especially codon groups 100 - 108 and 181 - 190). Patients failing on one NNRTI are very likely to possess multiple NNRTI resistance mutations. NNRTIs should always be used as part of a potent antiretroviral therapy to insure suppression of viral replication, thus circumventing the rapid selection of cross-resistant variants.
...
PMID:[Non-nucleoside reverse transcriptase inhibitors]. 1092 53

(+)-Calanolide A is a novel, naturally occurring, nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase first isolated from a tropical tree (Calophyllum lanigerum) in the Malaysian rain forest. Previous studies have demonstrated that (+)-calanolide A has specific activity against the reverse transcriptase of HIV-1 and a favorable safety profile in animals. In addition, (+)-calanolide A exhibits a unique HIV-1 resistance profile in vitro. The safety and pharmacokinetics of (+)-calanolide A was examined in four successive single-dose cohorts (200, 400, 600, and 800 mg) in healthy, HIV-negative volunteers. In this initial phase I study, the toxicity of (+)-calanolide A was minimal in the 47 subjects treated. Dizziness, taste perversion, headache, eructation, and nausea were the most frequently reported adverse events. These events were not all judged to be related to study medication nor were they dose related. While 51% of subjects reported mild and transient dizziness, in many cases this appeared to be temporally related to phlebotomy. Calculation of the terminal-phase half-life (t(1/2)) was precluded by intrasubject variability in the 200-, 400-, and 600-mg dose cohorts but was approximately 20 h for the 800-mg dose group. (+)-Calanolide A was rapidly absorbed following administration, with time to maximum concentration of drug in plasma (T(max)) values occurring between 2.4 and 5.2 h postdosing depending on the dose. Plasma levels of (+)-calanolide A at all dosing levels were quite variable; however, both the mean concentration in plasma (C(max)), and the area under the plasma concentration-time curve increased proportionately in relation to the dose. Although raw plasma drug levels were higher in women than in men, when doses were normalized for body mass, the pharmacokinetic profiles were virtually identical with those observed for males. In general, levels of (+)-calanolide A in human plasma were higher than would have been predicted from animal studies, yet the safety profile remained benign. In conclusion, this study demonstrated the safety and favorable pharmacokinetic profile of single doses of (+)-calanolide A in healthy, HIV-negative individuals.
...
PMID:Safety and pharmacokinetics of single doses of (+)-calanolide a, a novel, naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy, human immunodeficiency virus-negative human subjects. 1130 99

Four new drugs have been developed to overcome the limitations of the currently available anti-HIV drugs, including inconvenient schedules, side effects, and drug interactions. It is hoped that abacavir, efavirenz, adefovir dipivoxil, and amprenavir will be widely available in the near future. Abacavir, a nucleoside reverse transcriptase inhibitor with a twice-daily schedule, offers good bioavailability and generally mild side effects. Efavirenz, a non-nucleoside reverse transcriptase inhibitor with a once daily schedule, may produce side effects such as rash and dizziness. Adefovir dipivoxil, a nucleotide analog with once daily dosing, can cause carnitine depletion and carnitine supplementation is recommended. Amprenavir, a protease inhibitor with twice-daily dosing, has rather mild side effects. Information on efficacy, availability, and resistance for each of these drugs is given.
...
PMID:Antiretroviral agents: the next generation. 1136 27

Efavirenz (Sustiva), a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by DuPont Pharmaceuticals, was approved by the Food and Drug Administration. DuPont has promoted the once-daily efavirenz as being as equally effective as a protease inhibitor, and has priced it accordingly. The results from Study 006, the central trial for efavirenz, reported high antiviral activity, but had a significant dropout rate. This made it difficult to extrapolate the findings for those individuals remaining. The results of other key studies, such as Study 020 and ACTG 364, are discussed. Efavirenz is most effective when combined with protease inhibitors or nucleoside analogs. Some of the side effects of efavirenz are higher cholesterol levels, dizziness, and skin rashes. The possibility of birth defects has prompted DuPont to advise patients to use two types of birth control while taking efavirenz. A contact number is provided for physicians to register pregnant patients for follow-up if they have been exposed to efavirenz. Other protease-sparing options besides efavirenz are discussed, such as Nevirapine and Delavirdine.
...
PMID:Another expensive drug for your cocktail. 1136 6

The U.S. Food and Drug Administration (FDA) has approved Sustiva (efavirenz) as the first HIV drug to have a once-daily dosing schedule. The drug, developed by DuPont Pharmaceuticals, is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and will be used in combination with other anti-HIV drugs for both adult and pediatric patients. Results from clinical trials show that Sustiva reduces plasma viral loads to below quantifiable levels in a majority of treatment naive and experienced individuals in two, three, and four drug combinations. It can be taken with or without food, although high fat meals may interfere with absorption and should be avoided. The drug is generally well tolerated, with the most significant side effects being nervous system related, such as insomnia and dizziness. Mild to moderate skin rashes were also reported in one out of four patients. Women should not become pregnant while taking Sustiva because birth defects have been noted in animal studies. Contact information is provided.
...
PMID:FDA approves Sustiva (efavirenz) capsules, first once-daily anti-HIV drug. Food and Drug Administration. 1136 15

The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.
...
PMID:FDA approves efavirenz. Food and Drug Administration. 1136 87

A study of Triangle Pharmaceuticals' non-nucleoside reverse transcriptase inhibitor, Coactinon, found that the drug significantly suppressed viral replication when used with d4T and 3TC. The manufacturer reported mild side effects, including nausea, headache, dizziness, diarrhea, and rash.
...
PMID:Triangle Pharma Coactinon combo may suppress HIV. 1136 23

Stavudine administered once daily is a nucleoside analogue reverse transcriptase inhibitor. The efficacy (reduction in viral load and increase in CD4+ lymphocyte counts from baseline) of stavudine once daily-containing triple therapy was similar to that of stavudine immediate release (IR)-containing triple therapy in the treatment of antiretroviral-naive patients with HIV infection in two 48-week, randomised, double-blind trials. In the largest trial (n = 783), 80% of patients receiving stavudine 75 or 100mg once daily in combination with lamivudine 150mg twice daily and efavirenz 600mg once daily, and 75% of patients receiving stavudine IR 30 or 40mg twice daily-containing combination therapy, had HIV RNA levels reduced to below the limit of quantification at 48 weeks (<400 copies/ml; intent-to-treat analysis). These findings are supported by those from the smaller trial in 150 patients. Stavudine once daily triple therapy was well tolerated, with the incidence of adverse events being similar to that with stavudine IR. Grades 2-4 treatment related adverse events occurring in > or =3% of patients in either group were dizziness, rash, abnormal dream, headache, insomnia, fatigue and peripheral neurological symptoms. Peripheral neurological symptoms occurred in 3% of patients receiving long-term treatment with stavudine once daily and 6% of patients receiving stavudine IR in a combined analysis.
...
PMID:Stavudine once daily. 1246 9


1 2 Next >>

---