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)

There are 3 groups of drugs available for the treatment of patients with HIV disease. These are the nucleoside reverse transcriptase inhibitors ('nucleoside analogues') [zidovudine, didanosine, zalcitabine, lamivudine and abacavir]; the non-nucleoside reverse transcriptase inhibitors (nevirapine, delavirdine and efavirenz); and the protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir and amprenavir). The preferred initial regimen should reduce and maintain plasma HIV RNA below the level of detection. Presently, the regimen of choice consists of 2 nucleoside analogues plus a protease inhibitor with high in vivo efficacy. An alternative combination consists of 2 nucleoside analogues plus a non-nucleoside reverse transcriptase inhibitor. Drug interactions are one of the major problems associated with these multidrug regimens. Changes in plasma concentrations of the nucleoside analogues are unlikely to be of clinical relevance as drug effect is mainly dependent on the rate and extent of intracellular phosphorylation. Combinations of zidovudine plus stavudine, and probably zalcitabine plus lamivudine, should be avoided as competition for phosphorylating enzymes may occur. The antiviral efficacy of some nucleoside analogues, e.g. stavudine, may be compromised by prior treatment with other nucleosides (e.g. zidovudine). However, these data need to be clarified in further studies. It is unlikely that administration of other antiretrovirals will influence the activity of nucleoside analogues. Protease inhibitors are metabolised by hepatic cytochrome P450 (CYP) 3A4. Combination protease inhibitor therapy can result in drug interactions mediated by enzyme inhibition. Ritonavir is the most potent inhibitor, saquinavir the least. The protease inhibitors also interact with the non-nucleoside reverse transcriptase inhibitors. Nevirapine and efavirenz induce drug metabolising enzymes and may reduce plasma concentrations of protease inhibitors. A study in healthy volunteers showed that nelfinavir concentrations are increased by combination with efavirenz. Delavirdine inhibits drug metabolising enzymes and increases the plasma concentration of coadministered protease inhibitors. The nucleoside analogues would not be expected to interact with the protease inhibitors. Apart from the ability of didanosine to reduce the area under the concentration-time curve of delavirdine, there are no reports of clinically significant interactions of other antiretrovirals with the non-nucleoside reverse transcriptase inhibitors. Triple therapy is the current standard of care for patients with HIV disease. However, studies of quadruple therapy are already under way. Drug interactions are likely to remain one of the major considerations when selecting a therapeutic regimen for patients with HIV.
...
PMID:Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection. 1032 Sep 51

Nevirapine is the first member of a new therapeutic class (NNRTI: non nucleoside inhibitors of the reverse transcriptase) in the treatment against human immunodeficiency virus (HIV). In association with two other antiretroviral products, it reduces significantly the viral load and increases the CD4-cells-count, especially in naive patients. Results at six months show that a tritherapy including nevirapine and 2 nucleoside inhibitors of the reverse transcriptase (NRTIs) has a similar efficacy than an association including 1 anti-protease and two NRTIs. Nevirapine is easy to take (1 tablet 2x/day, irrespective of the meals). Its tolerance profile is favourable. The principal side effect is a rash, which can be severe in rare cases.
...
PMID:[Nevirapine (Viramune): a new HIV inhibitor]. 1033 4

A 31-year-old man with the acquired immunodeficiency syndrome who developed toxic epidermal necrolysis (TEN) was successfully treated with intravenous immunoglobulin. He presented with a widespread, blistering skin rash, extensive mucosal ulceration, high-grade fever and pancytopaenia. Nevirapine, a non-nucleoside reverse transcriptase inhibitor, was suspected as the culprit drug, although the patient had been taking this medication for 6 months. The patient also demonstrated an increased number of gamma/delta (gamma delta) T cells that decreased concomitantly with his clinical improvement. This correlation has not been described in TEN previously and may be of pathophysiological significance.
...
PMID:Toxic epidermal necrolysis in acquired immunodeficiency syndrome treated with intravenous gammaglobulin. 1043 28

Nevirapine (NVP), a non-nucleoside inhibitor of HIV-1 reverse transcriptase, is concomitantly administered to patients with a variety of medications. To assess the potential for its involvement in drug interactions, cytochrome P-450 (CYP) reaction phenotyping of NVP to its four oxidative metabolites, 2-, 3-, 8-, and 12-hydroxyNVP, was performed. The NVP metabolite formation rates by characterized human hepatic microsomes were best correlated with probe activities for either CYP3A4 (2- and 12-hydroxyNVP) or CYP2B6 (3-and 8-hydroxyNVP). In studies with cDNA-expressed human hepatic CYPs, 2- and 3-hydroxyNVP were exclusively formed by CYP3A and CYP2B6, respectively. Multiple cDNA-expressed CYPs produced 8- and 12-hydroxyNVP, although they were produced predominantly by CYP2D6 and CYP3A4, respectively. Antibody to CYP3A4 inhibited the rates of 2-, 8-, and 12-hydroxyNVP formation by human hepatic microsomes, whereas antibody to CYP2B6 inhibited the formation of 3- and 8-hydroxyNVP. Studies using the CYP3A4 inhibitors ketoconazole, troleandomycin, and erythromycin suggested a role for CYP3A4 in the formation of 2-, 8-, and 12-hydroxyNVP. These inhibitors were less effective or ineffective against the biotransformation of NVP to 3-hydroxyNVP. Quinidine very weakly inhibited only 8-hydroxyNVP formation. NVP itself was an inhibitor of only CYP3A4 at concentrations that were well above those of therapeutic relevance (K(i) = 270 microM). Collectively, these data indicate that NVP is principally metabolized by CYP3A4 and CYP2B6 and that it has little potential to be involved in inhibitory drug interactions.
...
PMID:Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. 1057 31

Nevirapine (NVP) is a potent noncompetitive inhibitor of the reverse transcriptase enzyme, which is necessary for HIV replication. NVP selectively inhibits HIV-1 but not HIV-2 and any of the human DNA polymerases. NVP is active against ZDV-resistant HIV-1 and synergistic with nonnucleoside reverse transcriptase inhibitors. NVP has a favorable pharmacokinetic profile, becomes widely distributed throughout body tissues including the central nervous system, and is active in the adult at an oral dose of 200 mg administered twice daily after a 2 week lead-in dose of 200 mg/day due to its long elimination half life. Although the currently used protease inhibitors (PIs) may undergo more rapid rates of metabolism because NVP induces CYP3A, No dosage adjustments are required when NVP is taken in combination with PIs so far. When administered in triple combinations with antiretroviral agents, the antiviral effect of NVP has been profound and sustained in HIV-infected patients, particularly in naive patients to antiretroviral therapy. Resistance to NVP is rapid when given as monotherapy, but this is altered and made less clinically relevant when NVP is administered as a triple combination. NVP has a safety profile that does not overlap with other antiretroviral therapies, the most common treatment-limiting reaction being rash. It seems that NVP would be a very useful option in combination with antiretroviral agents.
...
PMID:[Antiretroviral agent nevirapine: its pharmacological action and potential for clinical use]. 1058 33

Nevirapine is the first non nucleoside reverse transcriptase inhibitor registered in Belgium and indicated in the treatment of HIV-1 infection. In association with 2 nucleoside analogues, its efficiency is similar to a tritherapy with protease inhibitor, particularly in naive patients with low viral load. It has a good tolerance profile and is easy to take. Studies in progress should permit to widen its indications.
...
PMID:[Pharma-clinics. The drug of the month. Nevirapine. Viramune]. 1068 2

Nevirapine (VIRAMUNE) is a non-nucleoside reverse transcriptase inhibitor with activity against human immunodeficiency virus type 1 (HIV-1), currently marketed for the treatment of HIV-1 infected adults. A reverse phase HPLC-UV method was optimized and validated for the determination of nevirapine in human plasma, serum, milk and cerebrospinal fluid. The analyte was extracted from 250 microl of biofluid using a bonded silica solid phase extraction column, and resolved chromatographically on a reversed-phase, 15x0.46 cm i.d. 5 microm particle Supelco LC-8 analytical column with an isocratic mobile phase of 63% phosphate buffer (0.025 M, pH 6.0) with 1-butanesulfonic acid as anion-pair reagent: 21.5% methanol: 15.5% acetonitrile. The peaks were detected at a flow rate of 1.0 ml min(-1), at a wavelength of 280 nm, with a run time of 10 min. The assay was linear over a range of 25 to 10000 ng ml(-1). This method has been used for the clinical development of nevirapine.
...
PMID:HPLC-UV method for the quantitation of nevirapine in biological matrices following solid phase extraction. 1070 12

The aetiology of hepatic dysfunction in patients with HIV infection is multifactorial. Re-activation of hepatitis C infection, drug toxicity, and opportunistic infections are all potential causes. Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy for the treatment of HIV infection. It is associated with a significant incidence of hepatotoxicity, usually occurring in the initial month of therapy. We report the case of a 49-year-old man who developed NVP-induced prolonged hepatotoxicity 5 months after commencing antiretroviral therapy.
...
PMID:Late onset hepatitis and prolonged deterioration in hepatic function associated with nevirapine therapy. 1082 44

Nevirapine (Viramune), a dipyridiodiazepinone, is a potent and highly specific nonnucleoside inhibitor of HIV-1 reverse transcriptase. This paper describes the validation of a specific, sensitive, and stability-indicating high-performance liquid chromatography method for the assay and determination of related organic impurities in nevirapine drug substance. This method uses a Supelcosil LC-ABZ column, a mobile phase of 20:80 (v/v) acetonitrile-25mM NH4H2PO4 (pH 5.0), and ultraviolet detection at a wavelength of 220 nm. This method was validated for specificity, linearity, accuracy, repeatability, detection limit, quantitation limit, stability of analyte solutions, robustness, and intermediate precision. Nevirapine is completely separated from all impurities. The method is shown to be linear with coefficients of determination r2 greater than 0.999. Average accuracy is 100.4% with a relative standard deviation of 0.7% for the assay. Accuracy ranges from 100.1 to 102.6% for related organic impurities. Repeatability is good, with relative standard deviations not more than 1.4%. The detection limit and the quantitation limit are determined to be 0.001 and 0.003%, respectively. Relative response factors of known organic impurities are determined, permitting the use of nevirapine at the 0.1% level as an external standard for the quantitation of these impurities. Analyte solutions are shown to be stable for at least 2 days at ambient temperature. The method is validated as robust, and intermediate precision is high. A system suitability test is developed and validated, and requirements are set.
...
PMID:Validation of a high-performance liquid chromatography method for the assay of and determination of related organic impurities in nevirapine drug substance. 1089 Jul 48

(1) Nevirapine is the first non nucleoside inhibitor of HIV-1 reverse transcriptase to be marketed in France. (2) The clinical file comprises three comparative double-blind trials. One showed a better clinical benefit (in terms of disease progression or death) of a three-drug regimen comprising zidovudine, didanosine and nevirapine than with zidovudine + didanosine bitherapy. Two trials focusing on laboratory criteria (viral load and the CD4+ cell count) showed that a three-drug regimen of zidovudine + didanosine + nevirapine was more effective, after 12 months of treatment, than bitherapy with zidovudine + nevirapine or zidovudine + didanosine. (3) Occasionally severe cutaneous reactions are the main adverse effects of nevirapine. (4) Nevirapine is a liver enzyme inducer, hence the possibility of drug interactions, especially with protease inhibitors of HIV; the clinical consequences are poorly known.
...
PMID:Nevirapine: new preparation. In second-line triple-drug anti-HIV regimens. 1091 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---