Evidence map›Paper›PMID 17485498›Full record

ArticleAntimicrobial agents and chemotherapy2007

Pharmacokinetics of the anti-human immunodeficiency virus agent 1-(beta-D-dioxolane)thymine in rhesus monkeys.

Ghazia Asif, Selwyn J Hurwitz, Aleksandr Obikhod, David Delinsky, Janarthanan Narayanasamy, Chung K Chu, Harold M McClure, Raymond F Schinazi

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 46% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. 1,3-Dioxolane derived nucleos(t)ides: synthetic strategies, current position, and future promise in antiviral and anticancer drug discovery.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Ghazia AsifDepartment of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Selwyn J Hurwitz
Aleksandr Obikhod
David Delinsky
Janarthanan Narayanasamy
Chung K Chu
Harold M McClure
Raymond F Schinazi
Veterans Health Administration · USEmory University · USUniversity of Georgia · US

Funding

YNPRC NHP CLINICAL MEDICINE RESIDENCY PROGRAM - SUPPLEMENTP51RR000165 · NCRR · EMORY UNIVERSITY · PI JOHNS, MICHAEL M · 1985 to 2011
$114.0M
Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Hannah LF Cooper · 2002 to 2026
$74.0M
Synthesis and Biotransformation of Anti-HIV ProdrugsR37AI025899 · NIAID · UNIVERSITY OF GEORGIA (UGA) · PI CHU, CHUNG K · 2001 to 2010
$4.4M
NUCLEOSIDES WITH DUAL ANTI-HIV AND HBV ACTIVITYR37AI041980 · NIAID · EMORY UNIVERSITY · PI SCHINAZI, RAYMOND FELIX · 2000 to 2009
$2.1M
SYNTHESIS &EVALUATION OF ANTI-HIV NUCLEOSIDESR01AI032351 · NIAID · UNIVERSITY OF GEORGIA (UGA) · PI CHU, CHUNG K · 1992 to 2005
$1.7M
NCRR NIH HHS P51 RR000165NCRR NIH HHS RR0165NIAID NIH HHS 1P30-AI-42847NIAID NIH HHS 5P30-AI-50409NIAID NIH HHS 5R01-AI-32351NIAID NIH HHS 5R37-AI-25899NIAID NIH HHS 5R37-AI-41980NIAID NIH HHS P30 AI050409NIAID NIH HHS R01 AI032351NIAID NIH HHS R37 AI025899NIAID NIH HHS R37 AI041980
6 · The paper itself

Abstract

Beta-D-dioxolane-thymine (D-DOT) has potent and selective in vitro activity against several clinically important resistant human immunodeficiency virus (HIV) mutants and is in advanced preclinical development. Therefore, the single-dose intravenous and oral pharmacokinetics of D-DOT were studied with three rhesus monkeys. The pharmacokinetic profiles of D-DOT in serum and urine were adequately described by a two-compartment open pharmacokinetic model. D-DOT was rapidly and almost completely absorbed (absorption rate constant = 2.7 h(-1); fraction of oral dose absorbed = 0.82 to 1.06). The average serum beta half-life was 2.16 h. The average central and steady-state volumes of distributions were 0.52 and 1.02 liter/kg of body weight, respectively, and the average systemic and renal clearance values were 0.36 liter/h/kg and 0.18 liter/h/kg. Four or eight percent of administered D-DOT was eliminated in the urine as glucuronide within 8 h after intravenous or oral administration, respectively. D-DOT reached levels in the cerebrospinal fluid in excess of 10 to 20 times the median effective concentration for wild-type HIV and resistant mutants. The potent antiretroviral activity of D-DOT against a lamivudine- and zidovudine-resistant HIV-1 mutant, together with an excellent pharmacokinetic profile for rhesus monkeys, suggest that further development is warranted.

Indexed as

HIV-1Administration, OralAnimalsAntiviral AgentsArea Under CurveCalibrationChromatography, High Pressure LiquidDioxolanesFemaleHalf-LifeInjections, IntravenousMacaca mulattaMass SpectrometryMetabolic Clearance RateMolecular StructureReference StandardsAntiviral AgentsDioxolanesdioxolane-thymineThymine

Identifiers

PMID17485498
PMCPMC1913250
OpenAlexW2124396481

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.