ArticleClinical pharmacokinetics2023
Negative Impact of ST-Segment Elevation Myocardial Infarction and Morphine Dose on Ticagrelor Uptake and Pharmacodynamics: A Population PK/PD Analysis of Pooled Individual Participant Data.
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 6 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Effect of Alternative Administrations on P2Y12 Receptor Inhibitors' Pharmacokinetics and Pharmacodynamics: Systematic Review and Meta-Analysis.The AAPS journal · 2025Pooled it
- A population pharmacokinetic study of ampicillin therapy in hospitalized foals.Journal of veterinary internal medicine · 2026Article
- Evaluation of the Effect of Ticagrelor Dose Interruption and Treatment Resumption with or without Bolus Doses Through Population PK/PD Simulation.European journal of drug metabolism and pharmacokinetics · 2025Article
- Amikacin use in critically ill patients requiring renal replacement therapy: the AMIDIAL-ICU study.Annals of intensive care · 2025Article
- Oral P2YEuropean cardiology · 2025Review
- A Population Pharmacokinetic Model of Tocilizumab in Kidney Transplant Patients Treated for Chronic Active Antibody-Mediated Rejection: Comparison of Plasma Exposure Between Intravenous and Subcutaneous Administration Schemes.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTicagrelor is widely used in patients with stable and acute coronary artery disease. Understanding the factors that influence its pharmacokinetics (PK) and pharmacodynamics (PD) could improve therapeutic outcomes. We therefore performed a pooled population PK/PD analysis using individual patient data from two studies. We focused on the impact of morphine administration and ST-segment elevation myocardial infarction (STEMI) on the risk of high platelet reactivity (HPR) and dyspnea.
methodsA parent-metabolite population PK/PD model was developed based on data from 63 STEMI, 50 non-STEMI, and 25 chronic coronary syndrome (CCS) patients. Simulations were then run to evaluate the risk of non-response and adverse events associated with the identified variability factors.
resultsThe final PK model consisted of first-order absorption with transit compartments, distribution with two compartments for ticagrelor and one compartment for AR-C124910XX (active metabolite of ticagrelor), and linear elimination for both drugs. The final PK/PD model was an indirect turnover model with production inhibition. Morphine dose and STEMI, independently, had a significant negative effect on the absorption rate (reduction of log([Formula: see text]) by 0.21×morphine dose (mg) and by 2.37 in STEMI patients, both p < 0.001), and the presence of STEMI significantly impacted both efficacy and potency (both p < 0.001). The simulations run with the validated model showed a high rate of non-response in patients with those covariates (RR 1.19 for morphine, 4.11 for STEMI and 5.73 for morphine and STEMI, all three p < 0.001). By increasing ticagrelor dosage, the negative morphine effect was reversible in patients without STEMI and just limited in patients with STEMI.
conclusionThe developed population PK/PD model confirmed the negative impact of morphine administration and presence of STEMI on ticagrelor PK and antiplatelet effect. Increasing ticagrelor doses seems effective in morphine users without STEMI, whereas the STEMI effect is not entirely reversible.
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