Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1995 and 1996, the Food and Drug Administration (FDA) approved three products in the new protease inhibitor class of drugs--saquinavir (Invirase), ritonavir (Norvir), and indinavir (Crixivan). Another drug in this class of agents, nelfinavir (Viracept) (Agouron Pharmaceuticals), is expected to be available soon from the manufacturer through an expanded-access program. All four drugs, which inhibit HIV protease and thus interfere with viral maturation and replication, are the most potent antiretroviral agents available to treat patients with HIV disease. However, these protease inhibitors interact with rifamycin derivatives, such as rifampin and rifabutin, which are used to treat and prevent the mycobacterial infections commonly observed in HIV-infected patients. Rifamycins accelerate the metabolism of protease inhibitors (through induction of hepatic P450 cytochrome oxidases), resulting in subtherapeutic levels of the protease inhibitors. In addition, protease inhibitors retard the metabolism of rifamycins, resulting in increased serum levels of rifamycins and the likelihood of increased drug toxicity. This report describes approaches for managing patients who are candidates for or who are undergoing protease inhibitor therapy when tuberculosis (TB) is diagnosed and presents interim recommendations for managing these patients until additional data are available and formal guidelines are issued.
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PMID:Clinical update: impact of HIV protease inhibitors on the treatment of HIV-infected tuberculosis patients with rifampin. 892 17

Therapeutic drug monitoring is essential in HIV-patients undergoing highly active antiretroviral therapy (HAART). Saquinavir (SQV) is used alone or in combination with ritonavir (RTV) or nelfinavir (NLF), respectively, in the context of the HAART drug regimen. The achievable SQV concentration range in clinical practice remains to be elucidated. A non-randomized prospecitve clinical trial 19 patients (group I) receiving SQV (1x600 mg/d Invirase or Fortovase), 29 patients (group II) receiving SQV (2x600 mg/d Fortovase) plus RTV (2x400 mg/d Norvir), and 21 patients (group III) receiving SQV (2x600 mg/d Fortovase) plus NLF (2x750 mg/d Viracept) was conducted to determine SQV plasma concentrations. SQV levels were determined as trough levels during routine outpatient visits. Analysis was performed by HPLC with UV detection. The lowest SQV plasma levels were found in group I (95% CI 89-177 ng/ml). Significantly higher SQV levels were found in group III (combination with NLF) ranging from 242 to 398 ng/ml (95% CI) and in group II (combination with RTV) ranging from 1354 to 1747 ng/ml (95% CI). The IC 50% of 54 ng/ml was not reached in at least one sample during the study (mean duration of study 16+/-10 months) in 14/19 patients of group I, 9/29 patients in group II and 13/21 patients in group III, respectively. A positive correlation between patient compliance, defined by SQV levels in the 95% CI of the used combination, and the HIV RNA plasma level was found. The presented data confirm that therapy with SQV alone may not be effective, since trough levels are near the lower limit of antiretroviral efficacy. Although the combination of SQV with NLF results in higher SQV plasma concentrations in a bid regimen, in more than 60% of the patients SQV concentrations below IC 50 level were detected during the twelve-months study period. The combination of SQV with RTV yields the highest SQV-trough levels. SQV concentrations below the IC 50 were seen in only 31% of patients with the SQV/RTV combination. In conclusion, therapeutic drug monitoring allows an efficient surveillance of patients compliance. In addition, therapeutic drug monitoring represents a valuable tool for management of HAART in patients receiving a complex comedication or suffering from advanced liver disease.
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PMID:Therapeutic drug monitoring of saquinavir in patients during protease inhibitor therapy with saquinavir alone or in combination with ritonavir or nelfinavir. 1072 May 64

Nelfinavir mesylate (Viracept, formally AG1343) is a potent and orally bioavailable human immunodeficiency virus (HIV) type 1 (HIV-1) protease inhibitor (K(i) = 2 nM) and is being widely prescribed in combination with HIV reverse transcriptase inhibitors for the treatment of HIV infection. The current studies evaluated the presence of metabolites circulating in plasma following the oral administration of nelfinavir to healthy volunteers and HIV-infected patients, as well as the levels in plasma and antiviral activities of these metabolites. The results showed that the parent drug was the major circulating chemical species, followed in decreasing abundance by its hydroxy-t-butylamide metabolite (M8) and 3'-methoxy-4'-hydroxynelfinavir (M1). Antiviral assays with HIV-1 strain RF-infected CEM-SS cells showed that the 50% effective concentrations (EC50) of nelfinavir, M8, and M1 were 30, 34, and 151 nM, respectively, and that the corresponding EC50 against another HIV-1 strain, IIIB, in MT-2 cells were 60, 86, and 653 nM. Therefore, apparently similar in vitro antiviral activities were demonstrated for nelfinavir and M8, whereas an approximately 5- to 11-fold-lower level of antiviral activity was observed for M1. The active metabolite, M8, showed a degree of binding to human plasma proteins similar to that of nelfinavir (ca. 98%). Concentrations in plasma of nelfinavir and its metabolites in 10 HIV-positive patients receiving nelfinavir therapy (750 mg three times per day) were determined by a liquid chromatography tandem mass spectrometry assay. At steady state (day 28), the mean plasma nelfinavir concentrations ranged from 1.73 to 4.96 microM and the M8 concentrations ranged from 0.55 to 1.96 microM, whereas the M1 concentrations were low and ranged from 0.09 to 0.19 microM. In conclusion, the findings from the current studies suggest that, in humans, nelfinavir forms an active metabolite circulating at appreciable levels in plasma. The active metabolite M8 may account for some of the antiviral activity associated with nelfinavir in the treatment of HIV disease.
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PMID:Circulating metabolites of the human immunodeficiency virus protease inhibitor nelfinavir in humans: structural identification, levels in plasma, and antiviral activities. 1125 19

Agouron Pharmaceuticals, Inc. is starting two large studies of its protease inhibitor, Viracept, in HIV-infected persons with CD4 counts over 50 and a viral load of at least 15,000 copies. Viracept will be studied in combination with AZT plus 3TC vs. AZT plus 3TC alone.
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PMID:Agouron starts phase III protease inhibitor studies. 1136 85

Nelfinavir (Viracept) is a well-tolerated and effective protease inhibitor, especially when used in combination with nucleoside analogues. When used in triple combination, it is even more effective. An ongoing trial showed that 11 patients showed no detectable level of virus after 12 weeks, and after 20 weeks, there were no new HIV-related infections in the group. The trial is continuing.
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PMID:Another protease inhibitor proves highly effective. 1136 81

Many treatments highlighted at the ICAAC conference were designed to suppress the replication of HIV completely, but growing numbers of people are reporting rebound increases after initial decreases in viral load. However, new drugs are being developed which may be more effective, better tolerated, and less likely to lead to resistance. Agouron Pharmaceuticals has opened an expanded access program for its new protease inhibitor, Viracept; the program is open to people who cannot tolerate the other approved drugs. Gilead Sciences is warning physicians and patients that cidofovir should not be used with other kidney-toxic drugs.
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PMID:Anti-HIV agents at ICAAC. 1136 7

The Food and Drug Administration (FDA) approved nelfinavir (Viracept) for both adult and pediatric use for treatment of HIV infection when antiretroviral therapy is warranted. The drug is the fourth protease inhibitor to gain FDA approval. The recommended dose for adults is 750 mg three times daily, taken with food. The package insert warns of several potential drug interactions, and cautions that the most usual side effect is diarrhea. Developer Agouron Pharmaceuticals has established patient assistance programs to help patients pay for the medication, and are making the drug available through government discount programs.
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PMID:Nelfinavir (Viracept) approved: fourth protease inhibitor available. 1136 49

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the latest drugs used to treat HIV infection. Three NNRTIs are introduced: Viramune (nevirapine), Rescriptor (delavirdine), and Viracept (nelfinavir). Recommended doses, rates of absorption, side effects, distribution throughout the body, clinical studies, reactions with other drugs, and how the drugs are metabolized are given. A list of agents that may inhibit the effect of Rescriptor and Viracept, such as antihistamines, antibiotics and anti-convulsions, is presented.
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PMID:[New combination medications]. 1136 1

The Food and Drug Administration (FDA) is expected to grant accelerated approval for nelfinavir (Viracept) by mid-March 1997. Nelfinavir, a potent inhibitor of HIV replication when used in 3-drug therapies with AZT and 3TC, has produced undetectable viral loads and increased CD4 counts. A pediatric formulation has also been developed and the FDA has been asked to give it accelerated approval. An expanded access program is available that offers the drug free of charge to children aged 2 through 13 years. One of nelfinavir's advantages is that initial resistance to the drug does not also mean additional cross-resistance to the other protease inhibitors. A phone number is provided for further information.
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PMID:Nelfinavir (Viracept). 1136 28

The 1997 HIV/AIDS drugs are outlined and information is provided on their dosage, storage, efficacy, anti-viral effect, effect on T-cells, drug interactions, cross-resistance, cost, and availability. The drugs include Viramune (nevirapine), Rescriptor (delavirdine), and Viracept (nelfinavir).
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PMID:'96-'97 new drugs and the nominees for 1997 are.... 1136 66


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