Pharmacokinetics, pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y(12) receptor antagonist, in healthy subjects.
Purpose: Ticagrelor (AZD6140) is the first reversibly binding oral P2Y(12) receptor antagonist in development for reduction of clinical thrombotic events in patients with acute coronary syndromes. The purpose of our studies was to determine the effect of single-ascending doses of ticagrelor in healt...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 66; no. 5; pp. 487 - 497 |
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| Autores principales: | , |
| Formato: | clinical trial research tables/charts Journal Article |
| Publicado: |
Springer Nature
May2010
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105176889&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105176889 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: May2010 vid: 66 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 105176889 105176889 2010628751 10.1007/s00228-009-0778-5 NLM20091161 105176889 ppf: 487 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Pharmacokinetics, pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y(12) receptor antagonist, in healthy subjects. aug: au: Teng R Butler K affil: Clinical Pharmacology, AstraZeneca LP, OW3-117, 1800 Concord Pike, Wilmington, DE 19850-5437, USA sug: subj: Administration, Oral Platelet Aggregation Inhibitors Therapeutic Use Bleeding Time Methods Descriptive Statistics Female Human Male Pharmacy and Pharmacology Platelet Aggregation Inhibitors Pharmacodynamics Platelet Aggregation Inhibitors Pharmacokinetics Female Male ab: Purpose: Ticagrelor (AZD6140) is the first reversibly binding oral P2Y(12) receptor antagonist in development for reduction of clinical thrombotic events in patients with acute coronary syndromes. The purpose of our studies was to determine the effect of single-ascending doses of ticagrelor in healthy subjects. Methods: In two randomised, double-blind, placebo-controlled single ascending dose studies, healthy subjects received oral doses of 0.1-100 mg or placebo (n=25) and 30-400 mg or placebo (n=13). Results: Absorption of ticagrelor was rapid [median time to peak plasma concentration (t(max)) 1.3-2 h], as was the formation of its main (active) metabolite, AR-C124910XX (t(max) 1.5-3 h). For both ticagrelor and AR-C124910XX, the peak plasma concentration (C(max)) and area under the plasma concentration-time curve from time 0 to infinity (AUC0-[infinity]) increased in an apparently dose-proportional manner over the dose range studied, indicating linear pharmacokinetics. The mean terminal-phase half-life (t(½)) was approximately 7-8.5 h for ticagrelor and 8.5-10 h for AR-C124910XX; AR-C124910XX exposure was approximately one third that of ticagrelor. Inhibition of platelet aggregation (IPA) was dose related and was nearly complete at 2 h (mean 88-95%; final extent, with 20 µM adenosine diphosphate ADP) at doses of 100-400 mg. Conclusion: Linear and predictable pharmacokinetics of ticagrelor and AR-C124910XX were observed. A consistent and high IPA was maintained over 2-12 h, gradually decreasing with declining plasma concentration starting around 12 h post-dose, indicating that the IPA is reversible. Ticagrelor was well tolerated, with no serious or doserelated adverse events or notable changes in laboratory values observed. pubtype: Academic Journal doctype: clinical trial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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