Clinical Antiviral Activities

Hutcherson, S. L.

doi:10.1007/978-3-642-58785-6_15

Cited by 2 publications

(1 citation statement)

References 79 publications

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“…At the present time, parenteral delivery is the primary route for use in clinic, with intravenous infusion and subcutaneous injection the most extensively explored. Intradermal and intramuscular injection have been evaluated, and intraocular injection is being employed to treat an ocular infection with human cytomegalovirus (CMV) Hutcherson, 1998;Marwick, 1998). Inhalation is one route that is under nonclinical investigation for direct delivery of antisense oligonucleotides to the lung.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Toxicity Profile of a Phosphorothioate Oligonucleotide Following Inhalation Delivery to Lung in Mice

Templin

Levin²,

Graham³

et al. 2000

Antisense and Nucleic Acid Drug Development

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Antisense oligonucleotides are currently being investigated for the treatment of a variety of diseases. Antisense drugs are being administered primarily by parenteral injection. To explore more convenient patient delivery methods, we have characterized the tissue kinetics and tolerability of an inhaled aerosol formulation of a phosphorothioate oligonucleotide in mice. Concentrations of oligonucleotide in bronchioalveolar lavage fluid, plasma, and tissue and immunohistochemical localization were used to assess deposition and pharmacokinetic parameters. Significant concentrations of oligonucleotide in lung, as well as systemic tissues, were measured following a pulmonary dose of 12 mg/kg. Doses as low as 1-3 mg/kg also produced significant concentrations of oligonucleotide (>50 microg oligonucleotide per gram of tissue), and these were maintained in the lung with a halflife of 20 hours or greater. Oligonucleotide was localized to bronchiolar epithelium and alveolar epithelium and endothelium. Toxicity was mild at the 12 mg/kg level and minimal to absent at doses of 3 mg/kg or below. Based on a favorable pharmacokinetic profile and a relative lack of toxicity, inhalation delivery appears to be a therapeutic option for antisense oligonucleotides.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Toxicity Profile of a Phosphorothioate Oligonucleotide Following Inhalation Delivery to Lung in Mice

Templin

Levin²,

Graham³

et al. 2000

Antisense and Nucleic Acid Drug Development

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Current and Novel Agents for the Treatment of Cytomegalovirus Retinitis

Akerele

Lightman

1999

Drugs in R & D

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The incidence of cytomegalovirus (CMV) retinitis appears to be declining with improved treatment protocols for HIV and prophylaxis protocols for other high risk patients. Despite this, CMV retinitis remains a major cause of visual loss in patients who are severely immunocompromised. Treatment options are evolving in the light of viral resistance, new methods of drug delivery, new drugs, and the increased potential for improvement of immune function that modern antiretroviral therapy provides. In this article, we review the changing options available for the management of CMV retinitis and discuss possible therapeutic agents for the future.

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Clinical Antiviral Activities

Cited by 2 publications

References 79 publications

Pharmacokinetic and Toxicity Profile of a Phosphorothioate Oligonucleotide Following Inhalation Delivery to Lung in Mice

Pharmacokinetic and Toxicity Profile of a Phosphorothioate Oligonucleotide Following Inhalation Delivery to Lung in Mice

Current and Novel Agents for the Treatment of Cytomegalovirus Retinitis

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