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.
Are you sure you want to Unfollow 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 Blood pressure in relation to coffee and caffeine consumption Current Hypertension Reports, August 8, 2014    Review Article

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

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

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

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

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

7 A new “whey” to control diabetes American Friends of Tel Aviv University Medicine and Health News, August 6, 2014

8 Eating probiotics regularly may improve your blood pressure American Heart Association News, July 24, 2014

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

10 California trees nailed as the source of mystery infections Duke University Health & Medicine News, August 26, 2014

11 Egg consumption is associated with increased risk of ovarian cancer: Evidence from a meta-analysis of observational studies Clinical Nutrition, August 5, 2014    Evidence Based Medicine

12 First Chikungunya case acquired in the United States reported in Florida Full Text CDC, July 18, 2014    Free full text

13 Unprecedented number of medical staff infected with Ebola WHO news, August 27, 2014

14 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

15 Tea consumption and leukemia risk: A meta-analysis Tumor Biology, February 12, 2014    Evidence Based Medicine    Clinical Article

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

17 Nut consumption for vascular health and cognitive function Nutrition Research Reviews, July 14, 2014    Review Article

18 Soda consumption and risk of hip fractures in postmenopausal women in the Nurses’ Health Study American Journal of Clinical Nutrition, August 18, 2014    Clinical Article

19 The associations between yogurt consumption, diet quality, and metabolic profiles in children in the USA European Journal of Nutrition, July 22, 2014    Clinical Article

20 Effect and mechanisms of action of vinegar on glucose metabolism, lipid profile, and body weight Nutrition Reviews, September 3, 2014    Review Article

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

Register now to view all the MDLinx contents (FREE)!

  • Stay current on the latest literature, research and clinical news
  • Get special communications and offers from MDLinx and our sponsors
  • Receive invitations to paid market research
View Samples and Register

Connect with us, stay current.

Receive the latest mecial news
updates for free via email

Sign up!

Subscribe to our free RSS feeds:

Get the latest news in your specialty automatically added to your newsreader or your personal My Yahoo!, Google, My MSN or My AOL page. Learn More

Close