Phosphorylation of Nucleoside Analog Antiretrovirals: A Review for Clinicians

Nucleoside analogs (zidovudine, didanosine, zalcitabine, stavudine, abacavir, lamivudine) have been administered as antiretroviral agents for more than a decade. They undergo anabolic phosphorylation by intracellular kinases to form triphosphates, which inhibit human immunodeficiency virus replicati...

Full description

Saved in:
Bibliographic Details
Published in:Pharmacotherapy 2001-01, Vol.21 (1), p.11-34
Main Authors: Stein, Daniel S., Moore, Katy H. P.
Format: Article
Language:English
Subjects:
Animals
Anti-HIV Agents - metabolism
Anti-HIV Agents - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Antiviral Agents - metabolism
Antiviral Agents - pharmacology
Biological and medical sciences
Human immunodeficiency virus
Humans
Medical sciences
Pharmacology. Drug treatments
Phosphorylation
Retroviridae - drug effects
stavudine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Nucleoside analogs (zidovudine, didanosine, zalcitabine, stavudine, abacavir, lamivudine) have been administered as antiretroviral agents for more than a decade. They undergo anabolic phosphorylation by intracellular kinases to form triphosphates, which inhibit human immunodeficiency virus replication by competitively inhibiting viral reverse transcriptase. Numerous methods are used to elucidate the intracellular metabolic pathways of these agents. Intracellular and extracellular factors affect intracellular phosphorylation. Lack of standardization and complexity of methods used to study phosphorylation in patients limit interpretation of study results and comparability of findings across studies. However, in vitro and in vivo studies give important insights into mechanisms of action, metabolic feedback mechanisms, antiviral effects, and mechanisms of toxicity, and have influenced dosing regimens of nucleoside analogs.
ISSN:0277-0008
1875-9114
DOI:10.1592/phco.21.1.11.34439