title: Crushed sublingual versus oral ticagrelor administration strategies in patients with unstable angina. A pharmacokinetic/pharmacodynamic study.
abstract: Oral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina. Ticagrelor and its metabolite AR-C124900XX plasma concentration was evaluated in nine time points (time frame of 6 hours) using liquid chromatography coupled with mass spectrometry; platelet reactivity was evaluated using multiple electrode aggregometry. The area under the plasma concentration-time curve for ticagrelor and AR-C124900XX was significantly higher in patients treated with crushed tablets given orally compared with crushed tablets given sublingually only within the first hour after loading dose (936.9 ± 898.0 vs 368.0 ± 422.4, p=0.042 and 103.4 ± 120.8 vs 31.3 ± 43.9, p=0.031, respectively). Moreover, we showed significantly stronger platelet inhibition in patients receiving crushed ticagrelor orally vs. sublingually at 30 and 45 min after the loading dose (p=0.024 and p=0.016, respectively). Therefore, the administration strategy of ticagrelor determines the pharmacokinetic and pharmacodynamic profile of both ticagrelor and its active metabolite AR-C124900XX.
authors.affiliation: Piotr Niezgoda, MD, Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland, Tel.: +48 52 5854023, Fax: +48 52 5854024, E-mail: piotr.niezg@gmail.com.
authors.forename: Piotr
authors.initials: P
authors.lastname: Niezgoda
authors.forename: Joanna
authors.initials: J
authors.lastname: Sikora
authors.forename: Malwina
authors.initials: M
authors.lastname: Barańska
authors.forename: Adam
authors.initials: A
authors.lastname: Sikora
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Buszko
authors.forename: Emilia
authors.initials: E
authors.lastname: Siemińska
authors.forename: Michał Piotr
authors.initials: MP
authors.lastname: Marszałł
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Siller-Matula
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Alexopoulos
authors.forename: Tomasz
authors.initials: T
authors.lastname: Fabiszak
authors.forename: Jacek
authors.initials: J
authors.lastname: Kubica
mesh_terms: D065767:Activation, Metabolic; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000286:Administration, Sublingual; D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D019540:Area Under Curve; D004339:Drug Compounding; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011044:Poland; D011208:Powders; D058906:Purinergic P1 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D000077486:Ticagrelor; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D011208:Powders; D058906:Purinergic P1 Receptor Agonists; D013607:Tablets; D000077486:Ticagrelor; D000241:Adenosine
keywords: Ticagrelor; crushed ticagrelor administration; platelets; sublingual; unstable angina