Evidence map›Paper›PMID 36735213›Full record

ArticleClinical pharmacokinetics2023

Integrated Pharmacokinetics/Pharmacodynamics Model and Simulation of the Ticagrelor Effect on Patients with Acute Coronary Syndrome.

Zhiyan Liu, Yaou Liu, Guangyan Mu, Hanxu Zhang, Shuang Zhou, Zhe Wang, Qiufen Xie, Zining Wang, Ninghong Guo, Jie Huang and 9 more

Abstract readMulticenter Study
PubMed Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2023. 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
–field-weighted citation impact
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.

  1. Pooled it
  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

19 authors.

Zhiyan Liu *Department of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
Yaou Liu *Department of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
Guangyan MuDepartment of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
Hanxu ZhangDepartment of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
Shuang ZhouDepartment of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
Zhe WangDepartment of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
Qiufen XieDepartment of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
Zining WangDepartment of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
Ninghong GuoCenter of Clinical Pharmacology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China.
Jie HuangCenter of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, Hunan, China.
Liping GuoDepartment of Pharmacy, Zhengzhou Seventh People's Hospital, Zhengzhou, China.
Yan HuangDepartment of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
Jian LiCenter of Clinical Pharmacology, The Second Affiliated Hospital of Nanchang University, Jiangxi, China.
Guoping YangCenter of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, Hunan, China.
Dongdong YuanDepartment of Pharmacy, Zhengzhou Seventh People's Hospital, Zhengzhou, China.
Hongtao SongDepartment of Pharmacy, 900 Hospital of the Joint Logistics Team, Fuzhou, China.
Jie JiangDepartment of Cardiology, Peking University First Hospital, Beijing, China.
Qian XiangDepartment of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China. xiangqz@pkufh.com.
Yimin CuiDepartment of Pharmacy, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, China. cui.pharm@pkufh.com.ORCID 0000-0002-4186-1005

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundData available for pharmacokinetics (PK)/pharmacodynamics (PD) of ticagrelor and significant endogenous/exogenous factors or biomarkers related to bleeding events in both healthy and clinical patients are limited.

objectiveBased on PK and PD data from multicenter healthy subjects and patients, we aimed to establish an integrated approach towards population PK (pop PK) and the PD model of ticagrelor.

methodsThis study was conducted as a multicenter, prospective clinical registration study involving both healthy subjects and clinical patients. The integrated Pharmacokinetic/pharmacodynamic (PK/PD) models were characterized based on PK/PD [ticagrelor concentration, aggregation baseline (BASE), P2Y12 response unit (PRU) and inhibition rate (INHIBIT)] data from 175 healthy volunteers. The model was corrected by sparse PD (BASE, PRU and INHIBIT) data from 208 patients with acute coronary syndrome (ACS). The correlations between PD biomarkers and clinically relevant bleedings in 1 year were explored.

resultsA one-compartment, linear model with first-order absorption was adopted as PK model. Food status (FOOD) and body weight (WT) significantly influenced clearance and improved the fitting degree of the PK model, while SEX was selected as the covariates of the PD model. For patients taking ticagrelor 90 mg, the peak value [mean (95% CI)] of PRU was 355.15 (344.24-366.06) and the trough value was 3.64 (3.14-4.15). The PRU mean parameters were basically within the expected range (80-200) of the literature suggestions.

conclusionA fixed dose of ticagrelor, without adjusting the dosing regimen other than covariates of FOOD/WT/SEX, could be used in patients with acute coronary syndromes, and the standard regimen could be used in Chinese patients from the perspective of exposure.

Indexed as

Acute Coronary SyndromePlatelet Aggregation InhibitorsAdenosineHumansProspective StudiesPurinergic P2Y Receptor AntagonistsTicagrelorAdenosinePlatelet Aggregation InhibitorsPurinergic P2Y Receptor AntagonistsTicagrelor

Identifiers

What OpenQuestion holds

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Registered trials

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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.