Evidence map›Paper›PMID 27431234›Full record

Trial reportAntimicrobial agents and chemotherapy2016

Single-Ascending-Dose Pharmacokinetic Study of Tribendimidine in Opisthorchis viverrini-Infected Patients.

Urs Duthaler, Somphou Sayasone, Fiona Vanobbergen, Melissa A Penny, Peter Odermatt, Jörg Huwyler, Jennifer Keiser

Open access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.0field-weighted citation impact, top 16% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
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  5. Antimicrobial agents and chemotherapy · 2019
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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

7 authors at 3 institutions in 2 countries.

Urs DuthalerSwiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
Somphou SayasoneNational Institute of Public Health, Ministry of Health, Vientiane, Lao People's Democratic Republic.
Fiona VanobbergenSwiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
Melissa A PennySwiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
Peter OdermattSwiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
Jörg HuwylerDepartment of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland.
Jennifer KeiserSwiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland Jennifer.keiser@unibas.ch.
University of Basel · CHSwiss Tropical and Public Health Institute · CHMinistry of Health · LA

Funding

Medical Research Council G1100699Wellcome Trust
6 · The paper itself

Abstract

Praziquantel is the only drug available for the treatment of Opisthorchis viverrini infections. Tribendimidine has emerged as a potential treatment alternative; however, its pharmacokinetic (PK) properties have not been sufficiently studied to date. Via two phase IIa dose-finding studies, 68 O. viverrini patients were treated with 25- to 600-mg doses of tribendimidine using 50- and 200-mg tablet formulations. Plasma, blood, and dried blood spots (DBS) were sampled at selected time points. The two main metabolites of tribendimidine, active deacetylated amidantel (dADT) and acetylated dADT (adADT), were analyzed in plasma, blood, and DBS. PK parameters were estimated by noncompartmental analysis. An acceptable agreement among plasma and DBS concentrations was observed, with a mean bias of ≤10%, and 60% dADT and 74% adADT concentrations being within ±20% margins. We found that 200-mg tribendimidine tablets possess immediate floating characteristics, which led to variable time to maximal concentration of drug (Tmax) values (2 to 24 h) between individuals. Dose proportionality was observed for dADT from 25 to 200 mg using 50-mg tablets, but at higher dosages (200 to 600 mg), saturation occurred. The median ratio of the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) of dADT to the AUC0- 24 of adADT ranged from 0.8 to 26.4, suggesting substantial differences in acetylation rates. Cure rates ranged from 11% (25-mg dose) to 100% (400-mg dose). Cured patients showed significantly higher dADT maximal serum concentrations (Cmax) and AUC0-24 values than uncured patients. Tribendimidine is a promising drug for the treatment of opisthorchiasis. However, the tablet formulation should be optimized to achieve consistent absorption among patients. Further studies are warranted to assess the large differences between individuals in the rate of metabolic turnover of dADT to adADT. (This study has been registered with the ISRCTN Registry under no. ISRCTN96948551.).

Indexed as

AdolescentAdultAgedAnimalsAnthelminticsDried Blood Spot TestingDrug Administration ScheduleFemaleHumansMaleMiddle AgedOpisthorchiasisOpisthorchisPhenylenediaminesTandem Mass SpectrometryTreatment OutcomeAnthelminticsPhenylenediaminestribendimidine

Identifiers

PMID27431234
PMCPMC5038241
OpenAlexW2504864516

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.