Premium
Pharmacodynamics, pharmacokinetics, and safety of ticagrelor in Chinese patients with stable coronary artery disease
Author(s) -
Li Haiyan,
Guo Jingchuan,
Carlson Glenn F.,
Teng Renli
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12950
Subject(s) - ticagrelor , pharmacodynamics , medicine , pharmacokinetics , aspirin , coronary artery disease , pharmacology , anesthesia , clopidogrel
Aim The aim of the study was to assess ticagrelor's effects on inhibition of platelet aggregation (IPA), P2Y 12 reaction units (PRU, measure of platelet P2Y 12 receptor blockade), pharmacokinetic (PK) parameters and safety in Chinese patients with stable coronary artery disease (CAD). Methods This was an open label, single centre, randomized study. Thirty‐six patients on low dose aspirin (75–100 mg day –1 ) received ticagrelor 45, 60 or 90 mg (single dose, days 1 and 7; twice daily, days 3–6). IPA (final extent), PRU and ticagrelor and AR‐C124910XX plasma concentrations were determined. Results On day 1, peak IPA >80% occurred 2–6 h post‐dose (all doses). PRU was markedly reduced at 1 h vs . baseline (all doses). With ticagrelor 45 and 90 mg twice daily, maximum IPA (mean, SD) was 91% (13%), and 99% (3%), and maximum PRU reduction from baseline (mean, SD) was 82% (17%) and 92% (9%), respectively. Approximate dose‐proportional increases (mean [%CV]; 45 vs. 90 mg twice daily) in ticagrelor C max (616 [37] vs . 1273 [43] ng ml –1 ) and AUC (3882 [42] vs . 8206 [51] ng ml –1 h) and AR‐C124910XX parameters were seen. Pharmacodynamic and PK differences between 45 and 60 mg were small. No safety issues were identified. Conclusions In Chinese patients with CAD, ticagrelor (45, 60 and 90 mg) markedly reduced platelet aggregation. The IPA and PRU magnitude increased generally with increasing doses. However, the mean pharmacodynamic differences between 45 and 60 mg doses were small. Following single and multiple doses, the mean C max and AUC values of ticagrelor and AR‐C124910XX increased approximately dose proportionally between 45 and 90 mg doses.