Zidovudine

Bhana, Nila; Ormrod, Douglas; Perry, Caroline M.; Figgitt, David P.

doi:10.2165/00128072-200204080-00004

Cited by 13 publications

(4 citation statements)

References 196 publications

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“…Figure a shows that when zidovudine was administered subcutaneously as part of the hydrogel system, the plasma concentration initially peaked at 590 ng mL –1 1 h after administration. This concentration falls within the first 72 h of treatment with zidovudine, for which the IC 90 range is 30–130 ng mL –1 , up to the final time point of 35 days . Blood plasma concentrations of zidovudine were also found to be within four times its respective IC 90 value (120 ng mL –1 ), a pharmacokinetic benchmark for HIV protection .…”

Section: Results and Discussionmentioning

confidence: 80%

“…This concentration falls within the first 72 h of treatment with zidovudine, for which the IC 90 range is 30−130 ng mL −1 , up to the final time point of 35 days. 109 Blood plasma concentrations of zidovudine were also found to be within four times its respective IC 90 value (120 ng mL −1 ), a pharmacokinetic benchmark for HIV protection. 110 The initial peak in the plasma zidovudine concentration is likely due to burst release from the system upon administration during the gelation process as discussed in section 2.5 and displayed in Figure 3f.…”

Section: 7mentioning

confidence: 88%

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In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Coulter,

Pentlavalli,

et al. 2024

J. Am. Chem. Soc.

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Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proofof-concept for the development of a new optimized in situ forming injectable depot based on a tetrabenzylamine-tetraglycine-D-lysine-O-phospho-D-tyrosine peptoid-D-peptide formulation ((NPhe) 4 GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated. After subcutaneous injection, a hydrogel depot forms from the solubilized peptoid-peptide-drug formulation in response to phosphatase enzymes present within the skin space. This system is able to deliver clinically relevant concentrations of a model drug, the antiretroviral zidovudine (AZT), for 35 days in Sprague−Dawley rats. Oscillatory rheology demonstrated that hydrogel formation began within ∼30 s, an important characteristic of in situ systems for reducing initial drug bursts. Gel formation continued for up to ∼90 min. Small-angle neutron scattering data reveal narrow-radius fibers (∼0.78−1.8 nm) that closely fit formation via a flexible cylinder elliptical model. The inclusion of non-native peptoid monomers and D-variant amino acids confers protease resistance, enabling enhanced biostability to be demonstrated in vitro. Drug release proceeds via hydrolysis of an ester linkage under physiological conditions, releasing the drug in an unmodified form and further reducing the initial drug burst. Subcutaneous administration of (NPhe) 4 GGGGk(AZT)y(p)-OH to Sprague−Dawley rats resulted in zidovudine blood plasma concentrations within the 90% maximal inhibitory concentration (IC 90 ) range (30−130 ng mL −1 ) for 35 days.

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Section: Results and Discussionmentioning

confidence: 80%

Section: 7mentioning

confidence: 88%

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Coulter,

Pentlavalli,

et al. 2024

J. Am. Chem. Soc.

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“…3 -Azido-2 ,3 -dideoxythymidine (AZT), an inhibitor of the RNA directed DNA synthesis of the human immunodeficinecy virus (HIV), was the first drug commonly used in medicinal practice to treat HIV-1 [1,2]. In cells, this nucleoside is gradually phosphorylated to form 5 -triphosphate, which is incorporated into DNA and blocks viral DNA chain elongation because of the absence of 3 -hydroxyl terminus [14]. Though AZT has shown its efficiency and is still widely used in some cARTs [15], there is a greater tendency of RNA viruses toward mutagenesis, resulting in the formation of drug-resistant forms.…”

Section: Introductionmentioning

confidence: 99%

Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1

Glumakova,

Ivanov,

Vedernikova

et al. 2023

Pharmaceutics

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Nucleoside reverse transcriptase inhibitors are the first class of drugs to be approved by the FDA for the suppression of HIV-1 and are widely used for this purpose in combination with drugs of other classes. Despite the progress in HIV-1 treatment, there is still the need to develop novel efficient antivirals. Here the efficiency of HIV-1 inhibition by a set of original 5-substituted uridine nucleosides was studied. We used the replication deficient human immunodeficiency virus (HIV-1)-based lentiviral particles and identified that among the studied compounds, 2′,3′-isopropylidene-5-iodouridine was shown to cause anti-HIV-1 activity. Importantly, no toxic action of this compound against the cells of T-cell origin was found. We determined that this compound is significantly more efficient at suppressing HIV-1 compared to Azidothymidine (AZT) when taken at the high non-toxic concentrations. We did not find any profit when using AZT in combination with 2′,3′-isopropylidene-5-iodouridine. 2′,3′-Isopropylidene-5-iodouridine acts synergistically to repress HIV-1 when combined with the CDK4/6 inhibitor Palbociclib in low non-toxic concentration. No synergistic antiviral action was detected when AZT was combined with Palbociclib. We suggest 2′,3′-isopropylidene-5-iodouridine as a novel perspective non-toxic compound that may be used for HIV-l suppression.

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“…3-azido-3-deoxythymidine (AZT) was the first drug approved by the US Food and Drug Administration (FDA) for treatment of HIV-1 in adults and children (Bhana et al 2002; Vivet-Boudou et al 2006). AZT also reduces vertical transmission of HIV-1 during pregnancy by 70% (Connor et al 1994).…”

Section: Introductionmentioning

confidence: 99%

A Review of the Molecular Mechanisms of Chemically Induced Neoplasia in Rat and Mouse Models in National Toxicology Program Bioassays and Their Relevance to Human Cancer

et al. 2009

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Tumor response in the B6C3F1 mouse, F344 rat, and other animal models following exposure to various compounds provides evidence that people exposed to these or similar compounds may be at risk for developing cancer. Although tumors in rodents and humans are often morphologically similar, underlying mechanisms of tumorigenesis are often unknown and may be different between the species. Therefore, the relevance of an animal tumor response to human health would be better determined if the molecular pathogenesis were understood. The underlying molecular mechanisms leading to carcinogenesis are complex and involve multiple genetic and epigenetic events and other factors. To address the molecular pathogenesis of environmental carcinogens, we examine rodent tumors (e.g., lung, colon, mammary gland, skin, brain, mesothelioma) for alterations in cancer genes and epigenetic events that are associated with human cancer. Our NTP studies have identified several genetic alterations in chemically induced rodent neoplasms that are important in human cancer. Identification of such alterations in rodent models of chemical carcinogenesis caused by exposure to environmental contaminants, occupational chemicals, and other compounds lends further support that they are of potential human health risk. These studies also emphasize the importance of molecular evaluation of chemically induced rodent tumors for providing greater public health significance for NTP evaluated compounds.

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Zidovudine

Cited by 13 publications

References 196 publications

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1

A Review of the Molecular Mechanisms of Chemically Induced Neoplasia in Rat and Mouse Models in National Toxicology Program Bioassays and Their Relevance to Human Cancer

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