Pharmacokinetics and pharmacodynamics of ticagrelor in patients with stable coronary artery disease: results from the onset-offset and respond studies
Clinical Pharmacokinetics,  Clinical Article

Husted SE et al. – Ticagrelor pharmacokinetics in stable coronary artery disease (CAD) patients were comparable to previous findings in stable atherosclerotic and acute coronary syndromes (ACS) patients, and were not affected by prior clopidogrel exposure or clopidogrel responsiveness. Ticagrelor effectively inhibited platelet aggregation, and trough plasma concentrations of ticagrelor and AR–C124910XX were sufficient to result in high IPA in stable CAD patients.

Methods
  • Patients were treated with ticagrelor (180mg loading dose, 90mg twice daily maintenance dose) or clopidogrel (600mg loading dose, 75mg once daily maintenance dose) in addition to aspirin (acetylsalicylic acid) [75–100mg once daily].
  • Ticagrelor administration was for 6 weeks in ONSET–OFFSET.
  • In RESPOND, ticagrelor was given for 14 days before or after 2 weeks of clopidogrel in patients classified as clopidogrel responders or non–responders.
  • Pharmacokinetics and IPA were evaluated following the loading and last maintenance doses.
  • Exposure–IPA relationships were evaluated using a sigmoid maximum effect (Emax) model.
  • The outcome measures were ticagrelor and AR–C124910XX (active metabolite) pharmacokinetics and exposure–IPA relationships in both trials, including the effect of prior clopidogrel exposure, and effects in clopidogrel responders and non–responders in RESPOND.

Results
  • In ONSET–OFFSET, maximum (peak) plasma concentration (Cmax), time to Cmax (tmax) and area under the plasma concentration–time curve from time 0 to 8 hours (AUC8) for ticagrelor were 733ng/mL, 2.0 hours and 4130ng•h/mL, respectively; and for AR–C124910XX were 210ng/mL, 2.1 hours and 1325ng•h/mL, respectively.
  • Emax estimates were IPA >97%.
  • Trough plasma ticagrelor (305ng/mL) and AR–C124910XX (121ng/mL) concentrations were 5.2 and 7.7 times higher than respective concentration producing 50% of maximum effect (EC50) estimates.
  • In RESPOND, ticagrelor mean Cmax and AUC8 following 2–week dosing were comparable between clopidogrel responders (724ng/mL and 3983ng•h/mL, respectively) and non–responders (764ng/mL and 3986ng•h/mL, respectively).
  • Pharmacokinetics of ticagrelor were unaffected by prior clopidogrel dosing.
  • Emax estimates were IPA >96% for both responders and non–responders.
  • Trough plasma concentrations were sufficient to achieve high IPA.

Please login or register to follow this author.
► Click here to access PubMed, Publisher and related articles...
<< Previous Article | Next Article >>

Your Unread Messages in Nursing

See All >> Messages include industry-sponsored communications and special communications from MDLinx

Most Popular Nursing Articles

1 Yogurt consumption, weight change and risk of overweight/obesity: The SUN cohort study Nutrition, Metabolism & Cardiovascular Diseases, July 28, 2014    Clinical Article

2 Vitamin D and sleep disorders Full Text Nature and Science of Sleep, August 13, 2014    Free full text    Clinical Article

3 Blood pressure in relation to coffee and caffeine consumption Current Hypertension Reports, August 8, 2014    Review Article

4 Metformin in chronic kidney disease: Time for a rethink Peritoneal Dialysis International, July 9, 2014    Clinical Article

5 Suffering from constipation? Self-acupressure can help UCLA Health System, November 19, 2014

6 Effect of ginger (Zingiber officinale) on heavy menstrual bleeding: a placebo-controlled, randomized clinical trial Phytotherapy Research, October 13, 2014    Clinical Article

7 UAB plans clinical trial for repurposed drug shown to reverse diabetes UAB Medicine, November 12, 2014

8 Long-term associations of nut consumption with body weight and obesity American Journal of Clinical Nutrition, June 23, 2014    Clinical Article

9 Decreased ability to identify odors can predict death The University of Chicago Medical Center News, October 3, 2014

10 Chocolate intake and diabetes risk Clinical Nutrition, July 21, 2014    Clinical Article

11 Vitamin D and the risk of dementia and Alzheimer's disease Neurology®, August 27, 2014    Clinical Article

12 Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review and meta-analysis European Journal of Cancer, August 7, 2014    Review Article

13 Study identifies best way to treat neck pain Johns Hopkins Medicine, October 24, 2014

14 Yogurt and weight management American Journal of Clinical Nutrition, April 3, 2014    Review Article

15 Proton pump inhibitors decrease diversity in gut microbiome, increase risk for complications Mayo Clinic, November 25, 2014

16 'Tis the season to indulge in walnuts UC Davis Health System, November 17, 2014

17 Fish consumption and risk of gastrointestinal cancers: A meta-analysis of cohort studies Full Text World Journal of Gastroenterology, November 17, 2014    Free full text    Evidence Based Medicine

18 Associations of sugar and artificially sweetened soda and chronic kidney disease: A systematic review and meta-analysis Nephrology, September 24, 2014    Evidence Based Medicine    Review Article

19 Eating habits, body fat related to differences in brain chemistry Full Text NIH News, September 10, 2014    Free full text

20 Dairy product consumption and gastric cancer risk: A meta-analysis Full Text World Journal of Gastroenterology, November 14, 2014    Free full text    Evidence Based Medicine

Indexed Journals in Nursing: Journal of Advanced Nursing, Journal of Clinical Nursing, Nurse Education In Practicemore