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)

Amprenavir is a viral protease inhibitor with specificity for the HIV protease enzyme. The resistance profile of amprenavir appears to differ from that of other protease inhibitors such as saquinavir and indinavir. Twelve hours after single-dose administration of amprenavir 1200mg to HIV-infected individuals, the mean plasma concentration of the drug was more than 10-fold greater than the 50% inhibitory concentration for HIV-1IIIB in peripheral blood lymphocytes. In a small nonblind study, amprenavir monotherapy increased CD4+ cell count and decreased viral load in 37 patients with HIV infection and no previous exposure to protease inhibitor therapy. Combination therapy comprising amprenavir and other antiretroviral agents (abacavir, zidovudine, lamivudine, indinavir, saquinavir or nelfinavir) decreased viral load and increased CD4+ cell counts in patients with HIV infection. Antiviral efficacy was maintained during up to 24 weeks' follow-up. Available data suggest that rash, headache and diarrhoea or loose stools are the most frequent adverse events associated with amprenavir therapy.
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PMID:Amprenavir. 961 98

Amprenavir (141W94, VX-478, KVX-478) is metabolized primarily by CYP3A4 (cytochrome P450 3A4) in recombinant systems and human liver microsomes (HLM). The effects of ketoconazole, terfenadine, astemizole, rifampicin, methadone, and rifabutin upon amprenavir metabolism were examined in vitro using HLM. Ketoconazole, terfenadine, and astemizole were observed to inhibit amprenavir depletion, consistent with their known specificity for CYP3A4. The HIV protease inhibitors, indinavir, saquinavir, ritonavir, and nelfinavir, were included in incubations containing amprenavir to examine the interactions of HIV protease inhibitors in vitro. The order of amprenavir metabolism inhibition in human liver microsomes was observed to be: ritonavir > indinavir > nelfinavir > saquinavir. The Ki value for amprenavir-mediated inhibition of testosterone hydroxylation in human liver microsomes was found to be approximately 0.5 microM. Studies suggest that amprenavir inhibits CYP3A4 to a greater extent than saquinavir, and to a much lesser extent than ritonavir. Amprenavir, nelfinavir, and indinavir appear to inhibit CYP3A4 to a moderate extent, suggesting a selected number of coadministration restrictions.
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PMID:Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug interactions. 964 46

Amprenavir is a new peptidomimetic inhibitor of the HIV protease enzyme. Amprenavir has a twice daily dosing schedule and can be administered with or without food making it a convenient dosing regimen among the protease inhibitors (PIs). It is currently being investigated in combination with various nucleoside reverse transcriptase inhibitors (NRTIs) and initial results are promising. Amprenavir may also be useful for salvage therapy in patients failing PI-containing regimens as little cross-resistance has been observed so far with nelfinavir, indinavir or saquinavir. However, amprenavir resistant strains show cross-resistance with ritonavir. Clinical evidence indicates amprenavir is generally well tolerated. However, there is little information to date regarding the ability of amprenavir to cause lipodystrophy or other disturbances of lipid metabolism.
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PMID:Coming therapies: amprenavir. 1062 44

Amprenavir (Agenerase, 141-W94, VX-478) is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PRI) recently approved for the treatment of HIV-1 infection in the United States. A major cause of treatment failure is the development of resistance to PRIs. One potential use for amprenavir is as salvage therapy for patients for whom treatment that includes one (or more) of the other four currently approved PRIs-saquinavir, indinavir, ritonavir, and nelfinavir-has failed. We evaluated the cross-resistance to amprenavir of viruses that evolved during treatment with the two most commonly prescribed PRIs, nelfinavir and indinavir. Unexpectedly, a dramatic increase in susceptibility (2.5- to 12. 5-fold) was observed with 20 of 312 (6.4%) patient viruses analyzed. The most pronounced increases in susceptibility were strongly associated with an N88S mutation in protease. All viruses that carried the N88S mutation were hypersensitive to amprenavir. Site-directed mutagenesis studies confirmed the causal role of N88S in determining amprenavir hypersensitivity. The presence of the N88S mutation and associated amprenavir hypersensitivity may be useful in predicting an improved clinical response to amprenavir salvage therapy.
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PMID:A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir. 1075 56

Antiretroviral therapy may lead to decreased shedding of human immunodeficiency virus type 1 (HIV-1) in genital secretions. Thirty men, 19 receiving amprenavir and 11 receiving amprenavir, zidovudine, and lamivudine, donated blood and semen while undergoing treatment, to evaluate the effects of these medications on HIV-1 shedding in semen. Before therapy, 4 men had HIV-1 RNA levels in seminal plasma >6.0 log10 (1 million) copies/mL, markedly higher than levels in blood plasma. Most men (77%) had HIV-1 RNA levels in seminal plasma below the limit of quantification during therapy. Amprenavir alone suppressed HIV-1 RNA levels to <400 copies/mL in seminal plasma in the majority of patients, the first direct demonstration of the antiretroviral effects of a protease inhibitor in the male genital tract. However, 8 men (27%) had measurable HIV-1 in seminal plasma at their last study visit, 4 with increasing levels. Persistent replication of HIV in the genital tract may have implications for the selection of resistant virus and sexual transmission of HIV-1.
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PMID:The effects of protease inhibitor therapy on human immunodeficiency virus type 1 levels in semen (AIDS clinical trials group protocol 850). 1078 17

Amprenavir is a novel protease inhibitor with antiviral activity, and was approved in the U.S. (AGEN-ERASE) in 1999 for use in combination with other antiretrovirals for the treatment of HIV infection. The drug is developed by Kissei Pharmaceuticals Co., Ltd. in Japan, approved in the same year, and has been distributed by them (PROZEI). Amprenavir achieves a viral load of less than 400 copies/ml when it is given in triple combination therapy in both therapy-naive patients and patients previously treated with nucleoside reverse transcriptase inhibitors (NRTI). The recommended dose of amprenavir is eight 150-mg capsules, twice daily, or 1200 mg, b.i.d. Amprenavir may be taken with or without a meal; however, it should not to be taken with high-fat meals because its oral bioavailability may possibly be affected by fat. One of the major concerns associated with anti-HIV agents is the resistance mutation development, and the presence of I50V, M46I/L, I47V, I54L/V and I84V genotype has been observed in amprenavir therapy experienced subjects. Differences in resistance patterns and resistance mutation interactions may have amprenavir recognized as an alternative choice of drugs in maintaining efficacy. Therefore, amprenavir is believed to add an important treatment option in HIV infection therapy. It should be noted that P450 isozyme CYP3A4 is responsible for amprenavir; thus, care must be taken to avoid combined amprenavir with drugs that affect the action of CYP3A4, that act on the production CYP3A4 substrates, or that are metabolized by CYP3A4 metabolism. Amprenavir is the fifth protease inhibitor approved in Japan, and it is important to understand its differential and identical properties from other protease inhibitors to maximize its efficacy.
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PMID:[Pharmacological study and clinical effect of HIV protease inhibitor amprenavir]. 1123 98

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.
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PMID:Antiretroviral agents: the next generation. 1136 27

Since many new anti-HIV drugs are variations of currently available drugs, they may be more effective for people who are beginning treatment. One study shows favorable results when using efavirenz in triple combination therapy; however, it is recommended that this therapy be reserved for people who are treatment-naive and symptom-free. It is still unclear if all non-nucleoside RT inhibitors (NNRTIs) are as potent as efavirenz and whether the long-term potential for them is as promising as standard combinations. Researchers caution against pairing an NNRTI with a protease inhibitor in the event that resistance to the combination develops. That resistance may eliminate the option of using any other protease inhibitor or NNRTI in future therapies. Conversely, abacavir, an NARTI, has been effective in combination with many protease inhibitors. Amprenavir shows good antiviral activity; although studies show that it may not be successful as a salvage therapy with protease inhibitors. Nucleotide analogue reverse transcriptase inhibitors, such as adefovir and bis-poc PMPA, showed moderate anti-HIV potency. A study evaluating FTC alone showed a good reduction in viral load. FTC also fights hepatitis B and requires only one dose daily. Information is included about expanded access programs for abacavir, adefovir, and efavirenz.
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PMID:New drugs on the horizon. 1136 12

Several sessions at the 6th Conference on Retroviruses and Opportunistic Infections described the current state of pharmacology. Sessions were devoted to Zidovudine (AZT), Stavudine (d4T), and intracellular phosphorylation; the interactions between antiretrovirals and opiates; and Delavirdine (DLV) and Adefovir (ADV) interactions. Also addressed were the pharmacokinetics in patients with liver disease; the toxicities associated with Adefovir and Amprenavir (APV); and the uses of Hydroxyurea (HU).
Hopkins HIV Rep 1999 Mar
PMID:Pharmacology: a progress report. 1136 46

Amprenavir (Agenerase) received accelerated approval from the Food and Drug Administration (FDA) in April 1999. The protease inhibitor, developed by Vertex Pharmaceuticals and marketed by Glaxo Wellcome, is the 16th approved drug for HIV treatment. The capsules are taken twice daily, with or without food. Side effects and potential drug interactions are listed. Cross-resistance information is provided, along with data from earlier trials to demonstrate the drug's effectiveness against HIV. Contact information for Glaxo's patient assistance program is provided.
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PMID:Amprenavir (Agenerase). 1136 26


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