Disease relevance of VX-175

• Fosamprenavir: a review of its use in the management of antiretroviral therapy-naive patients with HIV infection [1].
• Fosamprenavir is one of the most recently approved HIV-1 protease inhibitors (PIs) and offers reductions in pill number and pill size, and omits the need for food and fluid requirements associated with the earlier-approved HIV-1 PIs [2].

High impact information on VX-175

• Once-daily (QD) fosamprenavir (FPV) at 1,400 mg boosted with low-dose ritonavir (RTV) at 200 mg is effective when it is used in combination regimens for the initial treatment of human immunodeficiency virus infection [3].
• Plasma Amprenavir Pharmacokinetics and Tolerability following Administration of 1,400 Milligrams of Fosamprenavir Once Daily in Combination with either 100 or 200 Milligrams of Ritonavir in Healthy Volunteers [3].
• Previous investigations have shown a significant negative two-way drug interaction between fosamprenavir (FPV) and lopinavir/ritonavir (LPV/RTV) in both human immunodeficiency virus (HIV)-infected patients and seronegative volunteers [4].
• Food does not affect the absorption of amprenavir following administration of the fosamprenavir tablet formulation; therefore, fosamprenavir tablets may be administered without regard to food intake [2].
• The pharmacokinetic properties of fosamprenavir and the first clinical trials in treatment-naive and treatment-experienced patients should allow it to be considered as a better alternative to amprenavir in countries where fosamprenavir is already available [5].

Chemical compound and disease context of VX-175

• Preclinical pharmacology and pharmacokinetics of GW433908, a water-soluble prodrug of the human immunodeficiency virus protease inhibitor amprenavir [6].
• High-dose combinations of fosamprenavir (FPV) and ritonavir (RTV) were evaluated in healthy adult subjects in order to select doses for further study in multiple protease inhibitor (PI)-experienced patients infected with human immunodeficiency virus type 1 [7].
• Pharmacokinetic interaction between Amprenavir/Ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation [8].

Biological context of VX-175

• Effect of antacids and ranitidine on the single-dose pharmacokinetics of fosamprenavir [9].
• Fosamprenavir (FPV) with and without ritonavir (RTV) was added to the antiretroviral regimens of human immunodeficiency virus-infected subjects receiving nevirapine (NVP) to evaluate this drug interaction [10].
• A high-yield synthesis of GW433908 is achieved by phosphorylation of the penultimate precursor of APV with phosphorous oxychloride (POCl(3)) in pyridine [6].
• Time-variant plasma amprenavir pharmacokinetics were observed with reductions in plasma amprenavir exposure over the first 4 weeks of dosing; the decrease in plasma amprenavir AUC(tau,ss) versus the AUC from 0 h to infinity was 27% for GW43308 1,395 mg, 45% for GW433908 1,860 mg, and 23% for amprenavir 1,200 mg [11].
• OBJECTIVE: To review the pharmacology, pharmacokinetics, virology, safety, efficacy, and clinical use of fosamprenavir [12].

Anatomical context of VX-175

• Taken together, these results suggest that GW433908 is primarily metabolized to APV at or in the epithelial cells of the intestine and that the prodrug is not substantially absorbed [6].
• Furthermore, GW433908 had poor transepithelial flux and APV showed significant flux across human-derived Caco-2 cell monolayers (a model of intestinal permeability) [6].
• Single-dose administration of GW433908 calcium salt in dogs and rats produced portal vein GW433908 concentrations that were maximally 1.72 and 0.79% of those of APV concentrations, respectively [6].

Associations of VX-175 with other chemical compounds

• Amprenavir-resistant viral isolates from patients experiencing treatment failure with fosamprenavir-based therapy in the NEAT study showed little or no cross-resistance to several other PIs, and protease mutations commonly selected for by various other PIs were not observed [1].
• OBJECTIVES: To evaluate the drug interaction between fosamprenavir (FPV) and esomeprazole (ESO) after repeated doses in healthy adults [13].
• DATA SOURCES: A MEDLINE (1966-July 2005) search was conducted using fosamprenavir, Lexiva, amprenavir, and GW433908 as key words [12].

Analytical, diagnostic and therapeutic context of VX-175

• Fosamprenavir was generally well tolerated in clinical trials [1].
• Fosamprenavir Clinical Study Meta-Analysis in ART-Na??ve Subjects: Rare Occurrence of Virologic Failure and Selection of Protease-Associated Mutations [14].

References