Evidence map›Paper›PMID 38244191›Full record

SynthesisClinical pharmacokinetics2024

Population Pharmacokinetic/Pharmacodynamic Models for P2Y12 Inhibitors: A Systematic Review and Clinical Appraisal Using Exposure Simulation.

Jingcheng Chen, Yuchen Qu, Muhan Jiang, Haiyan Li, Cheng Cui, Dongyang Liu

Abstract readSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. 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

6 authors at 2 institutions in 1 country.

Jingcheng ChenDepartment of Cardiology, Peking University Third Hospital, Beijing, 100191, China.
Yuchen QuDepartment of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Muhan JiangDrug Clinical Trial Center, Peking University Third Hospital, Beijing, 100191, China.
Haiyan LiDepartment of Cardiology, Peking University Third Hospital, Beijing, 100191, China.
Cheng CuiDepartment of Cardiology, Peking University Third Hospital, Beijing, 100191, China. cuicheng1226@163.com.
Dongyang LiuDrug Clinical Trial Center, Peking University Third Hospital, Beijing, 100191, China. liudongyang@vip.sina.com.ORCID 0000-0001-6446-0127
Peking University · CNSoochow University · CN

Funding

Bill & Melinda Gates Foundation INV-007625
6 · The paper itself

Abstract

BACKGROUND AND

objectiveRecent research indicates a correlation between plasma concentration of P2Y12 inhibitors and clinical events, particularly bleeding, which significantly impeded their clinical therapeutic performance. It is therefore vital to delve into the factors that might affect the plasma concentration. The study aims to summarize population pharmacokinetics/pharmacodynamics (PopPKPD) models for commonly prescribed P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) and assess bleeding risk in specific individual groups.

methodsThe PopPKPD models of P2Y12 inhibitors were collected and summarized based on predetermined inclusion and exclusion criteria. The collected models were replicated in simulations, which were used to assess factors affecting plasma concentrations of P2Y12 inhibitors. Simulation results for special populations were compared to therapeutic window based on reported exposure-effect relationships (PK/PD-related bleeding and thrombotic clinical outcomes) to predict bleeding risk in special populations with different dosing regimens and cumulative covariates.

resultFinally, 12 studies were included for PK simulation, 7 of which that also included PD data were subjected to further analysis, with the majority being based on Phase I or II trials. Simulations showed that several covariates such as female gender, weight, elderly can significantly impact on exposure, with special populations reaching up to 179% of the general population. However, after dose adjustment, blood concentrations for special populations can reach approximately ±20% of general population exposure. Therefore, lowering the maintenance dose of ticagrelor from 90 to 60 mg bid was first recommended to reduce bleeding risk without significantly increasing ischemic risk, particularly in elderly, small-weight Asian females.

conclusionLowering the maintenance dose of ticagrelor from 90 to 60 mg bid effectively reduces bleeding risk without increasing thrombotic infarction risk in elderly, small-weight Asian females.

Indexed as

Acute Coronary SyndromePurinergic P2Y Receptor AntagonistsAgedClopidogrelFemaleHemorrhageHumansMalePlatelet Aggregation InhibitorsPrasugrel HydrochlorideTicagrelorTreatment OutcomeClopidogrelPlatelet Aggregation InhibitorsPrasugrel HydrochloridePurinergic P2Y Receptor AntagonistsTicagrelor

Identifiers

PMID38244191
OpenAlexW4391051411

What Socratic 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 Socratic graph.