title: Effect of age and gender on pharmacokinetics and pharmacodynamics of a single ticagrelor dose in healthy individuals.
abstract: OBJECTIVE
  The aim of this study was to assess age and gender effects on ticagrelor pharmacokinetics and pharmacodynamics (PK/PD).
  
  
  METHODS
  Forty healthy individuals [18-45 years (young); ≥ 65 years (elderly); ten men, ten women per age group) received 200 mg ticagrelor.
  
  
  RESULTS
  Ticagrelor was rapidly absorbed [time to maximum concentration (C(max)) (t(max)) 2.5-3.0 h], and its major active metabolite, AR-C124910XX rapidly formed (t(max) 3.0-3.5 h) in all groups. Ticagrelor exposure was higher in elderly vs. the young [area under the curve from time 0 to infinity (AUC(0-∞)) 52%; C(max) 63% higher] and women vs. men (AUC(0-∞) 37%; C(max) 52% higher). Mean terminal elimination half-life was slightly longer in women vs. men but was unaffected by age. Similar results were observed for AR-C124910XX (elderly vs. young, AUC(0-∞) 48%; C(max) 61% higher), and in women vs. men (AUC(0-∞) 55%; C(max) 56% higher). Across all groups, ticagrelor produced substantial final-extent inhibition of platelet aggregation (IPA): >90% at 4 and 8 h postdose. Individuals with highest ticagrelor exposure (i.e., elderly) had the lowest IPA, indicating an age-related platelet sensitivity effect. In young individuals, platelet sensitivity was greater in men vs. women. Ticagrelor tolerability was not affected by age or gender.
  
  
  CONCLUSIONS
  Systemic exposures to ticagrelor and AR-C124910XX were higher in elderly vs. young and in women vs. men. Age- and gender-related changes in IPA were apparent, but substantial IPA was achieved in all groups. No adjustment in ticagrelor dose should be considered necessary based on age and gender.
authors.affiliation: Clinical Pharmacology, AstraZeneca LP, OW3-117, 1800 Concord Pike, PO Box 15437, Wilmington, DE 19850-5437, USA. renli.teng@astrazeneca.com
authors.forename: Renli
authors.initials: R
authors.lastname: Teng
authors.forename: Patrick
authors.initials: P
authors.lastname: Mitchell
authors.forename: Kathleen
authors.initials: K
authors.lastname: Butler
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012737:Sex Factors; D000077486:Ticagrelor; D055815:Young Adult
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine