Evidence map›Paper›PMID 25898809›Full record

Trial reportEuropean journal of drug metabolism and pharmacokinetics2016

Pharmacokinetics of IDX184, a liver-targeted oral prodrug of 2'-methylguanosine-5'-monophosphate, in the monkey and formulation optimization for human exposure.

Xin-Ru Pan-Zhou, Benjamin A Mayes, Hassan Rashidzadeh, Rahela Gasparac, Steven Smith, Sanjeev Bhadresa, Kusum Gupta, Marita Larsson Cohen, Charlie Bu, Steven S Good and 2 more

Abstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in European journal of drug metabolism and pharmacokinetics, 2016. 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
0.5field-weighted citation impact, top 35% 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, 5 citations in OpenAlex.

  1. Article
  2. Molecules (Basel, Switzerland) · 2024
    Review
  3. Review
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

12 authors at 1 institution in 1 country.

Xin-Ru Pan-ZhouIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA. xinru.panzhou@gmail.com.
Benjamin A MayesIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Hassan RashidzadehIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Rahela GasparacIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Steven SmithIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Sanjeev BhadresaIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Kusum GuptaIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Marita Larsson CohenIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Charlie BuIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Steven S GoodIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Adel MoussaIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Roger RushIdenix Pharmaceuticals, 320 Bent Street, 4th Floor, Cambridge, MA, 02141, USA.
Idera Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

IDX184 is a phosphoramidate prodrug of 2'-methylguanosine-5'-monophosphate, developed to treat patients infected with hepatitis C virus. A mass balance study of radiolabeled IDX184 and pharmacokinetic studies of IDX184 in portal vein-cannulated monkeys revealed relatively low IDX184 absorption but higher exposure of IDX184 in the portal vein than in the systemic circulation, indicating >90 % of the absorbed dose was subject to hepatic extraction. Systemic exposures to the main metabolite, 2'-methylguanosine (2'-MeG), were used as a surrogate for liver levels of the pharmacologically active entity 2'-MeG triphosphate, and accordingly, systemic levels of 2'-MeG in the monkey were used to optimize formulations for further clinical development of IDX184. Capsule formulations of IDX184 delivered acceptable levels of 2'-MeG in humans; however, the encapsulation process introduced low levels of the genotoxic impurity ethylene sulfide (ES), which necessitated formulation optimization. Animal pharmacokinetic data guided the development of a tablet with trace levels of ES and pharmacokinetic performance equal to that of the clinical capsule in the monkey. Under fed conditions in humans, the new tablet formulation showed similar exposure to the capsule used in prior clinical trials.

Indexed as

AnimalsCapsulesChemistry, PharmaceuticalGuanosineGuanosine MonophosphateHaplorhiniHumansLiverMaleProdrugsTablets7-methylguanosineCapsulesGuanosineGuanosine MonophosphateIDX184ProdrugsTablets2′-MeGEthylene sulfideIDX184Nucleotide prodrugPortal and systemic pharmacokinetics

Identifiers

PMID25898809
OpenAlexW1988013735

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.