title: Low-dose ticagrelor yields an antiplatelet efficacy similar to that of standard-dose ticagrelor in healthy subjects: an open-label randomized controlled trial.
abstract: Ticagrelor has a greater antiplatelet efficacy than clopidogrel but may be accompanied by an increased risk of bleeding. This study evaluated the antiplatelet effect and pharmacokinetic profile of low-dose ticagrelor in healthy Chinese volunteers. Thirty healthy subjects were randomized to receive standard-dose ticagrelor (180-mg loading dose, 90-mg twice daily [bid] [n = 10]), low-dose ticagrelor (90-mg loading dose, 45-mg bid [n = 10]), or clopidogrel (600-mg loading dose, 75-mg once daily [n = 10]). Platelet reactivity was assessed by using the VerifyNow P2Y12 assay at baseline and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours post-dosing. The ticagrelor and AR-C124910XX concentrations were measured for pharmacokinetic analysis. The percentage inhibition of P2Y12 reaction units was higher in the low-dose and standard-dose ticagrelor group than in the clopidogrel group at 0.5, 1, 2, 4, 8, and 48 hours post-dosing (P < 0.05 for all), but did not differ significantly between the two ticagrelor doses at any time-point (P > 0.05). The plasma ticagrelor and ARC124910XX concentrations were approximately 2-fold higher with standard-dose versus low-dose ticagrelor. No serious adverse events were reported. In conclusion, low-dose ticagrelor achieved faster and higher inhibition of platelet functions in healthy Chinese subjects than did clopidogrel, with an antiplatelet efficacy similar to that of standard-dose ticagrelor.
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Junmei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Center for Clinical Epidemiology and Evidence-based Medicine, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Quancai
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Xianxian
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Ma
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D002681:China; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine