External otitis: A challenge in management

Roland, Peter S.

doi:10.1007/s11908-000-0029-5

Cited by 8 publications

(1 citation statement)

References 45 publications

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“…Based on a number of successful studies in animal models (see Section 24.4.1), tenofovir and TDF are being considered as potential agents for chemoprophylaxis of HIV infection [139]. Recent exploratory clinical studies established the pharmacokinetics of tenofovir in the genital tract [140] and addressed the safety/tolerability of a tenofovir vaginal gel in both HIV-positive and negative women [141].…”

Section: Tenofovir Disoproxil Fumarate (Viread ò )mentioning

confidence: 99%

Tenofovir and Adefovir as Antiviral Agents

Cihlář

Delaney

Mackman

2008

Modified Nucleosides

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Over the past decade, nucleotide analogues have emerged as a novel class of clinically effective antiviral agents. Cidofovir was the first antiviral nucleotide to reach commercial approval for the treatment of cytomegalovirus retinitis in 1996. Subsequently, prodrugs of two closely related adenine nucleotide analogues -tenofovir and adefovir -have been licensed for the treatment of human immunodeficiency virus (HIV) and chronic hepatitis B virus (HBV) infections, respectively. Both tenofovir [(R)-9-(2-phosphonomethoxypropyl)adenine; PMPA] and adefovir [9-(2-phosphonomethoxyethyl)adenine; PMEA] ( Figure 24.1) are acyclic nucleoside phosphonates (ANPs), a structurally unique class of nucleotide analogues containing aliphatic sugar-like moieties, covalently attached to phosphonate groups.The concept of ANPs emerged during the mid-1980s [1] as a result of combining the early pursuits of bioisosteric nucleoside phosphonates [2, 3] with clinically validated antiviral acyclic nucleoside analogues such as acyclovir or ganciclovir. In contrast to antiviral nucleosides that require phosphorylation to their corresponding triphosphates in order to become active, two phosphorylation steps are sufficient for the metabolic activation of ANPs. Unlike the phosphate in natural nucleotides and phosphorylated nucleoside analogues (ÀCH 2 ÀOÀP linkage), the bioisosteric phosphonate moiety present in ANPs (ÀOÀCH 2 ÀP linkage) is resistant to enzymatic hydrolysis by phosphatases. Consequently, the active metabolites of ANPs (i.e., ANP diphosphates), which act through potent inhibition of viral polymerases, exhibit prolonged intracellular half-lives [4] and provide persistent antiviral effects [5]. The aliphatic linker mimicking the sugar part of nucleotides possesses multiple rotatable bonds, and offers a greater degree of flexibility to allow ANPs to maintain their potency against genetically diverse viral strains, including a range of drug-resistant viruses.Contrary to the vast majority of therapeutics, ANPs are quite hydrophilic due to two negative charges on their phosphonate moiety present at physiological pH. Although

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Section: Tenofovir Disoproxil Fumarate (Viread ò )mentioning

confidence: 99%