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Isentress

Manufactured by Merck Group
Sourced in United States

Isentress is a laboratory equipment product manufactured by Merck Group. It is designed to perform specific laboratory functions. No further details on the core function of Isentress can be provided while maintaining an unbiased and factual approach.

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5 protocols using isentress

1

Antiretroviral Formulated Food Protocol

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Food formulated with antiretroviral individual drug was prepared as reported with elevated dose modifications (34 (link)). In brief, tablets of emtricitabine and tenofovir disoproxil fumarate (Truvada®; Gilead Sciences) and raltegravir (Isentress®; Merck) were crushed into fine powder and manufactured with TestDiet 5B1Q feed (Modified LabDiet 5058 with 0.12% amoxicillin) into 1/2” irradiated pellets. Final concentrations of drugs in the food were 4,800 mg/kg raltegravir, 1,560 mg/kg tenofovir disoproxil, and 1,040 mg/kg emtricitabine. The estimated drug daily doses were 768 mg/kg raltegravir, 250 mg/kg tenofovir disoproxil, and 166 mg/kg emtricitabine.
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2

Exosome Therapy for HIV Latency

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Infected mice with detectable viremia were treated orally for two weeks with cART composed of drugs that block new infections. The cART regimen consisting of Truvada® [tenofovir disoproxil fumarate (TDF; 300 mg/tablet), emtricitabine (FTC; 200 mg/tablet) (Gilead Sciences)] and Isentress® [raltegravir (RAL; 400 mg/tablet) (Merck)], scaled down to the equivalent mouse dosage using the appropriate conversion factor, was administered in a drinking water formulation (sweetened water gel, Medidrop® Sucralose, ClearH20). For 200 ml Medidrop®, ½ Truvada tablet, and ½ Isentress tablet were crushed to powder, mixed by vigorous shaking, and changed weekly as per doses calculated previously64 . Mice were bled by retro-orbital bleeding, and peripheral blood cell populations and plasma viral loads were analyzed periodically using RT-qPCR. The oral cART regimen was withdrawn after two weeks and exosome treatment was initiated. Exosomes derived from HEK293T cells packed with nLuc, ZFP, or ZPAMt were retro-orbitally injected at a concentration of 100 × 109 in 100 ul sterile PBS once a week for 6 weeks.
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3

Antiretroviral Pharmacokinetics in Mice

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Female mice were administered RAL by oral gavage. The clinical formulation of the tablet (Isentress®: 400 mg, Merck & Co) was freshly dissolved in sterile PBS prior to oral gavage. The mouse equivalent dose was calculated by using an interspecies allometric scaling factor of 12.3 (31 (link),32 (link)). Mice received RAL (3.28 mg per 20 gram mouse) by oral gavage daily for 5 days. This dosing was same as we used in our previous PD study on RAL to determine its HIV prevention efficacy (16 (link)). Initial experiment included 5 mice per time point. Additional mice (2 (link)–3 (link)) were tested for the time points and compartments for which RAL concentration was below limit of quantification or showed high degree of variability in the initial study. Plasma and vaginal, rectal and intestinal tissue samples were collected following the last gavage at 2h, 8h, and 24h. In addition, 48h plasma samples were collected from one group of treated animals. All samples except 48h blood plasma were terminal and were collected during mouse necropsies. Tissue and plasma samples were snap frozen in liquid nitrogen within five minutes from the time of collection. For negative controls, plasma and tissue samples were collected from untreated mice and were processed using the protocols described above. All samples were stored at −80° C prior to drug concentration analysis.
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4

Bioequivalence of Raltegravir Tablets in Healthy Indian Subjects

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The validated method was applied to quantify plasma RAL concentration for a bioequivalence study in 18 healthy Indian subjects after oral administration of test (400 mg tablets) and a reference (ISENTRESS®, 400 mg raltegravir tablets from Merck & Co., Inc. Whitehouse Station, NJ 08889, USA) formulation under fasting conditions. Written consent was taken from all the subjects after informing them about the objectives and possible risks involved in the study. The study was conducted as per the International Conference on Harmonization, E6 Good Clinical Practice guidelines [30] . Blood samples were collected at 0.0 (pre-dose), 0.33, 0.67, 1.00, 1.25, 1.50, 1.75, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0 and 36.0 h after oral administration of test and reference formulations in labeled K3EDTA-vacutainers. Plasma was separated through centrifugation and kept frozen at −70 °C until analysis.
An incurred sample reanalysis was also done by reanalysis of 87 subject samples (10% of total subject samples analyzed) [31] (link). The selection criterion was based on samples which were near the Cmax and the elimination phase in the pharmacokinetic profile of the drug.
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5

Oral ART Treatment in HIV-Infected Mice

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Infected mice with detectable viral infection (defined as >103 cp/mL of HIV in blood) were treated orally for 3 weeks with ART composed of drugs that block new infections, without inhibiting viral production in infected cells. The ART regimen consisting of Truvada (tenofovir disoproxil fumarate [300 mg/tablet], emtricitabine [200 mg/tablet; Gilead Sciences, Foster City, CA]) and Isentress (raltegravir 400 mg/tablet (Merck, Kenilworth, NJ), scaled down to the equivalent mouse dosage using the appropriate conversion factor, was administered in a drinking water formulation (sweetened water gel, Medidrop Sucralose, ClearH20). For 400 mL Medidrop, ½ Truvada tablet, and ½ Isentress tablet were crushed to powder and mixed by shaking bottle to a homogenous solution; medicated water was changed weekly. Doses of ART drugs were calculated based on previous studies using the same delivery system.64 (link)
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