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It is administered intravenously as a bolus followed by continuous infusion. However, the dosage recommendations in the United States (US) and European Union (EU) differ considerably. Furthermore, in routine clinical practice, deviations from the recommendations may occur. The objective of the present study was to investigate the impact of different alterations on tirofiban plasma concentrations in US and EU administration regimens and to give suggestions for delay management in clinical practice. We therefore mathematically simulated the effects of different bolus-infusion delays and infusion interruptions in different scenarios according to the renal function. Here, we provide a systematic assessment of concentration patterns of tirofiban in the US versus EU dosage regimens. We show that differences between the two regimens have important effects on plasma drug levels. Furthermore, we demonstrate that deviations from the proper administration mode affect the concentration of tirofiban. Additionally, we calculated the optimal dosage of a second bolus to rapidly restore the initial concentration without causing overdosage. In conclusion, differences in tirofiban dosing regimens between the U.S and EU and potential infusion interruptions have important effects on drug levels that may impact on degrees of platelet inhibition and thus antithrombotic effects. Thus, the findings of our modelling studies may help to explain differences in clinical outcomes observed in previous clinical trials on tirofiban.<\/jats:p>","DOI":"10.1007\/s11239-022-02654-0","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T12:03:42Z","timestamp":1651147422000},"page":"301-308","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens"],"prefix":"10.1007","volume":"54","author":[{"given":"Nadia","family":"Heramvand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2856-6893","authenticated-orcid":false,"given":"Maryna","family":"Masyuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna M.","family":"Muessig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir M.","family":"Nia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasios","family":"Karathanos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amin","family":"Polzin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Valgimigli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A.","family":"Gurbel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Udaya S.","family":"Tantry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malte","family":"Kelm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"2654_CR1","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1056\/NEJM199201233260406","volume":"326","author":"V Fuster","year":"1992","unstructured":"Fuster V, Badimon L, Badimon JJ et al (1992) The pathogenesis of coronary artery disease and the acute coronary syndromes (1). 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Gurbel reports grants and personal fees from Bayer HealthCare LLC, Otitopic Inc, Amgen, Janssen, Medicure, and US WorldMeds LLC; grants from Instrumentation Laboratory, Haemonetics, Medicure Inc, Idorsia Pharmaceuticals, and Hikari Dx; personal fees from UpToDate. Paul A. Gurbel is a relator and expert witness in litigation involving clopidogrel. In addition, Paul A. Gurbel holds two patents, Detection of restenosis risk in patients and Assessment of cardiac health and thrombotic risk in a patient. Nadia Heramvand reports a grant from Medicure Inc. Marco Valgimigli reports research grants to the Inselspital from Medicure Inc. for the conduct of the FABOLUS FASTER Trial.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}