Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens

Abstract

AbstractTirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic treatment in patients with acute coronary syndromes (ACS) or high-risk percutaneous coronary interventions (PCI). 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.