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Topic: Protease inhibitor (pharmacology)

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	protease inhibitor - HighBeam Encyclopedia
		protease inhibitor, any of a class of drugs that interfere with replication of the AIDS virus (HIV), by blocking an enzyme (protease) necessary in the late stages of its reproduction.
		Clinical trials of the protease inhibitor indinavir have shown it to be especially beneficial in combination with the anti-HIV drugs AZT and 3TC, which act by blocking a different enzyme, reverse transcriptase.
		Protease inhibitor combination therapy and decreased condom use among gay men.
	www.encyclopedia.com /doc/1E1-proteas.html (341 words)

	Protease inhibitor (pharmacology) - Wikipedia, the free encyclopedia
		Protease inhibitors (PIs) are a class of medication used to treat or prevent infection by viruses, including HIV and Hepatitis C.
		Protease inhibitors have been developed or are presently undergoing testing for treating various viruses:
		Protease inhibitors were the second class of antiretroviral drugs developed.
	en.wikipedia.org /wiki/Protease_inhibitor_(pharmacology) (375 words)

	SF AIDS Fdn: BETA Year-End 99 -- Antiretroviral Pharmacology: Issues and Management
		Protease inhibitors act on the HIV protease enzyme, which functions as "molecular scissors" to cleave large precursor polyproteins at the end of the HIV life cycle.
		Many protease inhibitors have food restrictions and need to be taken either with food (saquinavir [Invirase, Fortovase], ritonavir, and nelfinavir [Viracept]) or on an empty stomach or with a low-fat meal (indinavir).
		Inhibitors are drugs that impair drug metabolism, decreasing clearance of substrate drugs and thus increasing their blood levels.
	www.sfaf.org /treatment/beta/b42/b42pharmacology.html (2790 words)

	Protease Inhibitor Drug Interactions -- BETA:9/97 - AEGIS
		Protease inhibitors may also cause increased levels of rifampin and rifabutin, potentially resulting in toxic side effects.
		Stopping a protease inhibitor may result in the development of drug resistance and may preclude later use of that drug.
		Protease inhibitors in patients with HIV disease: clinically important pharmacokinetic considerations.
	www.aegis.com /pubs/beta/1997/BE970907.htm (3554 words)

	Infectious Disease News: Cost of protease inhibitors may guide their use
		MIAMI — Protease inhibitors offer new hope to people with AIDS, but their cost may be a deciding factor in their use.
		Protease inhibitors interfere with an enzyme needed to manufacture key core proteins that enable virus particles to become infectious.
		If protease inhibitors indeed help to delay disease progression and prolong lives among people outside of clinical trials, then the increased cost of anti-HIV treatment might be made up by reducing costs associated with treating AIDS-related illnesses, including the cost of hospitalizing patients.
	www.infectiousdiseasenews.com /199606/protease.asp (1553 words)

	EMD Biosciences - Calbiochem - Inhibitors: Technical Tips
		The amount of inhibitor required depends on various factors, such as target accessibility, cell permeability, duration of incubation, type of cells used, etc. It is best to survey the literature to determine the initial concentration.
		The CHO-based inhibitors are reversible due to the fact that the thiol group of the enzyme forms an adduct to the carbonyl group of the aldehyde that is reversible.
		Serine proteases are widely distributed in all cells, bacterial cells contain higher levels of serine and metalloproteases; animal tissue extracts are rich in serine-, cysteine-, and metalloproteases, and plant extracts contain higher quantities of serine and cysteine proteases.
	www.emdbiosciences.com /html/cbc/IS_technical_tips.htm (1409 words)

	HIV Report January 2000 - What's in a Trough? Therapeutic Drug Monitoring (Site not responding. Last check: 2007-10-13)
		A dose-response relationship exists for HIV protease inhibitor monotherapy in which higher doses of drug are associated with a more durable suppression of viral load and probably less chance of the virus becoming resistant to the drug.
		For most HIV protease inhibitors, even when used in combination with nucleoside analogs, there appears to be a measurable relationship between some pharmacokinetic parameters (usually area under the concentration-time curve [AUC] or trough concentration [Cmin]) and viral load suppression.
		For reverse transcriptase inhibitors, the evidence for a reproducible concentration-response relationship is similarly problematic and complicated by the requirement for intracellular activation of nucleoside analogues.
	hopkins-aids.edu /publications/report/jan00_4.html (1879 words)

	StereoGraphics Success Stories - SmithGlaxoKline (Site not responding. Last check: 2007-10-13)
		Eric Furfine, GSK's protease research project leader, sought to show the investigators conducting the clinical trials the biochemical and structural characteristics of the HIV protease inhibitor as it bound to wild-type (WT) and drug-resistant HIV protease.
		HIV protease inhibitors are critical in the fight against AIDS as they work by blocking a part of HIV called protease.
		He explained that the objectives are to research protease inhibitor options with reduced pill burden and offer improved or unique resistance profiles from other inhibitors currently available.
	www.stereographics.com /news_about_us/success_stories/smithg.html (436 words)

	HIVresistanceWeb - Perspectives and Opinions - Dual PI therapy: Are all combinations good?
		The success of recent trials of combination protease inhibitor therapy using saquinavir and ritonavir has led some researchers to speculate that a dual protease combinations will be the wave of the future for HIV therapy.
		Combinations of protease inhibitors that do not have overlapping resistance mutation profiles would be expected to delay the emergence of resistance.
		For patients, a combination of two protease inhibitors that are antagonistic with a value of 1.7 is still better than protease monotherapy.
	www.hivresistanceweb.com /protected/po/bp-98apr-dualpi.shtml (565 words)

	Vertex’s Protease Inhibitor To Be Evaluated As Single Agent (Site not responding. Last check: 2007-10-13)
		Lynne Brum, Vertex's director of corporate communications, said development of the protease inhibitor, VX-478, is aimed at using the drug with other antiviral agents, such as Glaxo's FDA-approved reverse transcriptase inhibitors, AZT and 3TC.
		Three protease inhibitors already are on the market and Agouron Pharmaceuticals Inc., of La Jolla, Calif., expects to file for approval of its drug next year.
		Other protease inhibitors are given three times a day and must be taken in the presence or absence of food.
	www.pslgroup.com /dg/c65a.htm (755 words)

	Introduction (Site not responding. Last check: 2007-10-13)
		Protease inhibitors are the latest addition to the arsenal of drugs designed to combat the HIV virus.
		Protease inhibitors were not available at that time, so it would have been very unlikely that these subjects received protease inhibitor treatment prior to the sequence analysis study.
		Instead of having to develop resistant strains through mutations after the onset of protease inhibitor selective pressures, HIV resistant viruses are already present in the viral population prior to the onset of therapy.
	www.stanford.edu /~siegelr/philhsu.htm (3300 words)

	Tipranavir: New Protease Inhibitor Approved by the FDA for Patients With Extensive Treatment-Experience (Site not responding. Last check: 2007-10-13)
		Summary: Virologic responders were defined in the study as patients with at least 1 log reduction from baseline in HIV viral load: 40% of the patients receiving tipranavir/r achieved this goal vs 18% of the patients receiving different protease inhibitor regimens (boosted by ritonavir).
		The individually pre-selected protease inhibitor based on genotypic testing and the patient's medical history was lopinavir in 50%, amprenavir in 26%, saquinavir in 20% and indinavir in 4% of patients.
		Tipranavir co-administered with 200 mg of ritonavir at the recommended dosage is a net inhibitor of CYP 3A and may increase plasma concentrations of agents that are primarily metabolized by CYP 3A.
	www.hivdent.org /drugs1/drugTNPI0605.htm (3304 words)

	The Amyloid Proteins of Alzheimer's Disease as Potential Targets for Drug Therapy
		Additionally, a sequence for an inhibitor of the Kunitz family of serine protease inhibitors has been identified which is encoded by a sequence of the beta amyloid protein precursor messenger RNA.
		Thus, once a relevant protease is demonstrated for Alzheimer's disease, it is likely that an inhibitor could be developed relatively rapidly, based on the prior experience of the pharmaceutical industry with this class of drugs.
		NCO-700, an inhibitor of calcium-dependent neutral protease, is being evaluated for use in blocking proteolysis of myocardial proteins associated with myocardial infarction.
	www.dmso.org /articles/alzheimers/alzheim2.htm (2983 words)

	Protein Pump Keeps AIDS Drug Out
		In 1995, it became the first HIV protease inhibitor to gain approval by the Food and Drug Administration.
		The study was conducted by Dr. Terrence Blaschke, professor of medicine (clinical pharmacology), Dr. Branimir Sikic, professor of medicine (oncology and clinical pharmacology), oncology research biologist George Duran and postdoctoral fellow Carla Washington.
		None of the current HIV protease inhibitors gets into the brain, and P-glycoprotein lining the blood vessels in the brain may be responsible for keeping them out, Blaschke speculates.
	mednews.stanford.edu /releases/1997/marreleases/protease.html (977 words)

	Project Inform's PI Perspective 32 [ HIV / AIDS Treatment Information ]
		For instance, it is known that some protease inhibitors decrease the level of estrogen among women receiving hormone replacement or oral contraceptives, whereas the protease inhibitor indinavir (Crixivan) and the NNRTI efavirenz (Sustiva) increases the level of estrogen.
		Practically speaking, women on protease inhibitors should be counseled on how to alter the dose of their oral contraceptives or hormone replacement therapy to maintain effectiveness and/or use alternative methods of birth control.
		Additionally, this also suggests that some protease inhibitors might decrease the natural level of estrogen in women, leading to other potential health considerations associated with low estrogen levels (such as early menopause and/or loss of bone density).
	www.projinf.org /pip/32/pip32i.html (658 words)

	The intracellular pharmacology of antiretroviral protease inhibitors -- Ford et al. 54 (6): 982 -- Journal of ...
		Intracellular accumulation of protease inhibitors in subpopulations of lymphocytes with P-glycoprotein expression.
		Effect of alpha1-acid glycoprotein on the intracellular accumulation of the HIV protease inhibitors saquinavir, ritonavir and indinavir in vitro.
		HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter.
	jac.oxfordjournals.org /cgi/content/full/54/6/982 (4781 words)

	ScienceDaily: HIV-1 Protease Inhibitors: Effective Against Malaria?
		Science Daily — Protease inhibitors used to treat HIV-1 infection may also be effective for treatment or prevention of malaria, according to a study published in the December 1 issue of The Journal of Infectious Diseases, now available online.
		New Protease Inhibitor Could Thwart AIDS Resistance To Current Drugs (February 4, 1999) -- Researchers have developed a new protease inhibitor effective against mutating strains of the human AIDS virus that are resistant to current drugs, according to a just-released report in the...
		New Class Of Protease Inhibitors May Be Effective In Treating One Of Latin America's Most Devastating Diseases (August 20, 1998) -- Researchers at the San Francisco Veterans Affairs Medical Center and UC San Francisco have demonstrated that a type of drug known as a cysteine protease inhibitor may be highly effective against...
	www.sciencedaily.com /releases/2004/11/041123100855.htm (1790 words)

	Invirase Online, Description, Chemistry, Ingredients - Saquinavir Mesylate - RxList Monographs
		HIV protease is an enzyme required for the proteolytic cleavage of viral polyprotein precursors into individual functional proteins found in infectious HIV.
		Saquinavir in combination with the protease inhibitors amprenavir, atazanavir, or lopinavir resulted in synergistic antiviral activity.
		Six of the 22 isolates (27%) remained susceptible to all 4 protease inhibitors, 12 of the 22 isolates (55%) retained susceptibility to at least one of the PIs and 4 out of the 22 isolates (18%) displayed broad cross-resistance to all PIs.
	www.rxlist.com /cgi/generic/saquin.htm (881 words)

	Update on HIV Pharmacology and Therapeutic Drug Monitoring
		Protease inhibitor combinations based on the ability of drugs like ritonavir to increase concentrations of the paired drug through pharmacokinetic interactions are increasingly used in treatment.
		The use of the inhibitory quotient is motivated by the predictive value for virologic response of protease inhibitor trough concentrations in some studies.
		For reliable inhibitory quotients, comparative data for the different protease inhibitor combinations and other drugs need to be generated under identical experimental conditions.
	hivinsite.ucsf.edu /InSite.jsp?page=md-04-01-15 (2439 words)

	Project Inform: Drug Levels and HIV [ HIV / AIDS Treatment Information ]
		TDM may be particularly useful for protease inhibitors as their blood levels can vary greatly among individuals as there are differences in how people break down (metabolize) these drugs.
		Early results suggest that ritonavir is able to boost the levels of two protease inhibitors at the same time, indicating that this may possibly be a useful strategy for third line therapy.
		Practically speaking, women on protease inhibitors should be counseled on how to alter the dose of their oral contraceptives or HRT to maintain effectiveness and/or use other methods of birth control.
	www.projinf.org /fs/druglevels.html (2500 words)

	FDA Approves LEXIVA (fosamprenavir): study results for teatment naive & experienced, safety, adverse events, ...
		Amprenavir exhibited synergistic anti-HIV-1 activity in combination with the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir, didanosine, and zidovudine, and the protease inhibitor (PI) saquinavir, and additive anti-HIV-1 activity in combination with the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine and Pis indinavir, lopinavir, nelfinavir, and ritonavir in vitro.
		Coadministration of protease inhibitors, including LEXIVA, with St. John's wort is expected to substantially decrease protease inhibitor concentrations and may result in suboptimal levels of amprenavir and lead to loss of virologic response and possible resistance to LEXIVA or to the class of protease inhibitors.
		In a clinical study of LEXIVA used as the sole protease inhibitor, rash occurred in 2 of 10 patients (20%) with a history of sulfonamide allergy compared with 42 of 126 patients (33%) with no history of sulfonamide allergy.
	www.natap.org /2003/oct/102303_1.htm (5294 words)

	Pharmainfo.net - Nobel Hiv-1 Protease Inhibitors (Site not responding. Last check: 2007-10-13)
		The HIV protease is essential for viral infectivity and cleaves the viral polyprotein (gag-pol) into active viral enzymes (reverse transcriptase, protease and integrase) and structural proteins.
		Therefore, there is always a need for newer protease inhibitors for the effective treatment of HIV infections.
		It is a pro-drug of amprenavir, an inhibitor of HIV protease.
	www.pharmainfo.net /exclusive/reviews/nobel_hiv-1_protease_inhibitors (1332 words)

	Pharmacy Update -- May/June 97 (Site not responding. Last check: 2007-10-13)
		The approval of this agent, as with other protease inhibitors, is primarily based on surrogate markers of immunological (CD4 cell count) and virological (viral burden) response to therapy, when used in combination with nucleoside reverse transcriptase inhibitors (NRTIs).
		Since reported studies with all marketed protease inhibitors enrolled different patient populations, used various combinations of concomitant NRTIs, and utilized different viral load assays for determining virological responses, it is not possible to directly compare the results from these studies.
		Selection of which protease inhibitor(s) is (are) most appropriate for an individual patient should be based on the patientÍs prior experience with protease inhibitors, history of drug tolerance, potential drug-drug interactions, and dosing convenience.
	www.cc.nih.gov /phar/updates/97mayjun.html (2418 words)

	ROI CONFERENCE: Abacavir With Protease Inhibitors Results Potent Against HIV (Site not responding. Last check: 2007-10-13)
		The study, presented at the Fifth Conference on Retroviruses and Opportunistic Infections, evaluated abacavir in combination with the investigational protease inhibitor amprenavir (formerly 141W94, VX-478), as well as with each of the four currently available protease inhibitors (indinavir, nelfinavir, saquinavir soft gel caps and ritonavir).
		Amprenavir appears to be a highly potent protease inhibitor which is being studied with nucleoside analogues and together with other protease inhibitors.
		In contrast with currently available protease inhibitors which are dosed three times daily, amprenavir is being studied for twice daily dosing.
	www.pslgroup.com /dg/572AA.htm (870 words)

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