Evidence map›Paper›PMID 30761579›Full record

ArticleBritish journal of clinical pharmacology2019

A semiphysiological population pharmacokinetic model of agomelatine and its metabolites in Chinese healthy volunteers.

Feifan Xie, An Vermeulen, Pieter Colin, Zeneng Cheng

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06120543 (Correlation Between CYP1A2, ABCB1, CYP2C9 Gene Polymorphisms and Plasma Concentration of Agomelatine and Its Metabolites in Adult Patients With Depression), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-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.

NCT06120543 unknown statusnot on this mapstarted 2023, after this paper: background citation

Correlation Between CYP1A2, ABCB1, CYP2C9 Gene Polymorphisms and Plasma Concentration of Agomelatine and Its Metabolites in Adult Patients With Depression

TypeobservationalSponsorAffiliated Hospital of Nantong UniversityRan2023 to 2025Enrolled50ConditionsPolymorphism, Genetic, Depression, CYP1A2 Polymorphism, CYP2C9 Polymorphism
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
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  4. Review
  5. 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

4 authors at 3 institutions in 3 countries.

Feifan XieLaboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.ORCID 0000-0001-8427-4030
An VermeulenLaboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Pieter ColinLaboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.ORCID 0000-0003-3616-5539
Zeneng ChengResearch Institute of Drug Metabolism and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.ORCID 0000-0001-9352-9744
Ghent University Hospital · BECentral South University · CNUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsAgomelatine is an antidepressant for major depressive disorders. It undergoes extensive first-pass hepatic metabolism and displays irregular absorption profiles and large interindividual variability (IIV) and interoccasion variability of pharmacokinetics. The objective of this study was to characterize the complex pharmacokinetics of agomelatine and its metabolites in healthy subjects.

methodsPlasma concentration-time data of agomelatine and its metabolites were collected from a 4-period, cross-over bioequivalence study, in which 44 healthy subjects received 25 mg agomelatine tablets orally. Nonlinear mixed effects modelling was used to characterize the pharmacokinetics and variability of agomelatine and its metabolites. Deterministic simulations were carried out to investigate the influence of pathological changes due to liver disease on agomelatine pharmacokinetics.

resultsA semiphysiological pharmacokinetic model with parallel first-order absorption and a well-stirred liver compartment adequately described the data. The estimated IIV and interoccasion variability of the intrinsic clearance of agomelatine were 130.8% and 28.5%, respectively. The IIV of the intrinsic clearance turned out to be the main cause of the variability of area under the curve-based agomelatine exposure. Simulations demonstrated that a reduction in intrinsic clearance or liver blood flow, and an increase in free drug fraction had a rather modest influence on agomelatine exposures (range: -50 to 200%). Portosystemic shunting, however, substantially elevated agomelatine exposure by 12.6-109.1-fold.

conclusionsA semiphysiological pharmacokinetic model incorporating first-pass hepatic extraction was developed for agomelatine and its main metabolites. The portosystemic shunting associated with liver disease might lead to significant alterations of agomelatine pharmacokinetics, and lead to substantially increased exposure.

Indexed as

Models, BiologicalAcetamidesAdministration, OralAntidepressive AgentsArea Under CurveAsian PeopleBiological Variation, PopulationCross-Over StudiesFemaleHealthy VolunteersHumansLiverLiver Function TestsMajor Depressive DisorderMaleMetabolic Clearance RateAcetamidesagomelatineAntidepressive AgentsNaphthalenesTabletsagomelatinefirst-passmetabolitepharmacokineticssemiphysiological

Identifiers

PMID30761579
PMCPMC6475681
OpenAlexW2914163007

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Registered trials

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.