Regorafenib BAY 73-4506 of each drug are released from the vaginal rings over a 28 day

gh maraviroc is a licensed therapeutic, a significant body of data support the safety of maraviroc delivered orally. This is the first clinical study utilizing maraviroc in women for vaginal use. The maraviroc vaginal ring contains 100mg of maraviroc, and the combination vaginal ring contains Regorafenib BAY 73-4506 an additional 25 mg dapivirine, dispersed in a platinum catalysedcured silicone matrix. In vitro, similar amounts of each drug are released from the vaginal rings over a 28 day period despite the four fold difference in initial concentration, suggesting a lower solubility of maraviroc in silicone. The rationale for developing microbicides containing combinations of ARVs is discussed later in this chapter. Tenofovir vaginal ring, film and tablet Tenofovir is a nucleotide reverse transcriptase inhibitor approved for the treatment of HIV infection.
51 In addition mk-2866 Androgen Receptor inhibitor to 1% tenofovir gel, currently being tested in a phase III confirmatory efficacy trial for coitally associated use, other dosage forms of tenofovir are also under development.52 A polyurethane based tenofovir vaginal ring, designed to release at least 10 mg tenofovir daily over several months to help improve adherence, is planned to enter phase I clinical testing in 2012. Additional formulations in development include a fast dissolving film and tablet, which both have potential economic and acceptability advantages over the gel dosage form. Council, carrageenan based gel formulations of MIV 150 were shown to protect against vaginal challenge with a SHIV RT when applied topically 30 mins before vaginal challenge.
54 Although 2weeks of daily application of 50 M MIV 150 protected over 50% of macaques from infection for up to 8 h ON-01910 after last use, the combination of low dose MIV 150 and zinc acetate provided complete protection from infection for at least 24 h.55 DS 003 DS 003 is a highly potent molecule, one of a series of entry inhibitors discovered at Bristol Myers Squibb that binds tightly to the viral envelope glycoprotein gp120.56 58 This binding likely interferes with the interaction of HIV gp120 with the CD4 receptor on the host cell and prevents initial virus attachment. By acting at the earliest time of viral exposure, before interaction with its target cells, gp120 inhibitors have a strong potential to inhibit initial viral infection as vaginally delivered microbicides.
59 One compound of this class, Bristol Myers Squibb 378806, has been shown to neutralise a broad range HIV 1 clades and subtypes with minimal cytotoxicity.56 Bristol Myers Squibb 806 has also been shown to protect macaques against vaginal SHIV challenge.60 Licensed by Bristol Myers Squibb to the International Partnership for Microbicides in 2005 to develop into a microbicide for global use, DS003 has also been shown to broadly neutralise HIV 1 as well as viral infection of ex vivo genital explants with much higher potency than Bristol Myers Squibb 806. Preliminary studies indicate that DS003 has no genotoxicity, no evidence of sensitisation in guinea pigs, and no local or systemic toxicity in either rats or rabbits at intravaginal doses up to 25% weight/ weight. Given its mechanism of action, DS003 will need to be active in the aqueous environment of the vagina to prevent HIV transmission. Strategies for optimal delivery of DS00

Leave a Reply

Your email address will not be published. Required fields are marked *


You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>