Pharmacodynamics and pharmacokinetics of single doses of prasugrel 30 mg and clopidogrel 300 mg in healthy chinese and white volunteers: An open-label trial

Small, David S.; Payne, Christopher D.; Kothare, Prajakti A.; Yuen, Eunice; Natanegara, Fanni; Loh, Mei Teng; Jakubowski, Joseph A.; Lachno, D. Richard; Li, Ying G.; Winters, Kenneth J.; Farid, Nagy A.; Ni, Lan; Salazar, Daniel E.; Tomlin, Molly; Kelly, Raymond P.

doi:10.1016/j.clinthera.2010.02.015

Cited by 45 publications

(30 citation statements)

References 16 publications

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“…Following administration, the exposure to prasugrel's active metabolite following administration was higher in Asian groups than in previously reported studies comparing Asian and Caucasian groups [5,6] . The lower mean body weight of Asian subjects compared to Caucasian subjects may contribute to the higher exposure of prasugrel's active metabolite in Asians.…”

Section: Discussioncontrasting

confidence: 49%

“…Studies on healthy Caucasian and Chinese subjects suggested that Pras-AM exposure was higher in Chinese subjects than that in Caucasians [5] ; the study in Chinese, Korean, and Japanese populations also showed higher exposure to Pras-AM and higher degree of platelet inhibition in these groups than in Caucasian populations [6] .…”

Section: Acta Pharmacologica Sinica Npgmentioning

confidence: 99%

“…The LD (dose received on d 1) was 60, 30, or 30 mg, and the MD (dose received once daily on d 2 through 11) was 10, 7.5, or 5 mg. The dosing regimens were based on other trials that identified higher overall exposure and an elevated overall PD response in Asian versus Caucasian subjects in addition to subgroup analyses by ethnicity, body weight, and age [5][6][7] . The drug was supplied as a tablet containing 5, 7.5, or 10 mg of prasugrel as a hydrochloride salt.…”

Section: Subjectsmentioning

confidence: 99%

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Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects

et al. 2012

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Aim: To characterize the pharmacokinetics (PKs), pharmacodynamics (PDs), and tolerability of different dose regimens of prasugrel in healthy Chinese subjects. Methods: This was a single-centered, open-label, parallel-design study. Subjects received a single loading dose (LD) of prasugrel followed by once-daily maintenance dose (MD) for 10 d. They were enrolled into 3 groups: 60 mg LD/10 mg MD; 30 mg LD/7.5 mg MD; 30 mg LD/5 mg MD. Blood samples were collected after the first and last dose. The serum concentration of the active metabolite of prasugrel was determined using a LC/MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y 12 assay. Results: Thirty-six healthy native Chinese subjects (19 males) aged 18-45 were enrolled; mean age and body weight were similar across the treatment groups (n=12 for each). The metabolite AUC 0-4 and C max increased dose-proportionally across the dose range of 5 mg to 60 mg. The median T max was 0.5 h in all groups. The PD parameters, indicated by the inhibition of ADP-induced platelet aggregation, were met more rapidly in the 60 mg group than the 30 mg group after the LD (94%-98%). This high degree of inhibition of platelet aggregation was maintained following the 10 mg MD (87%-90%) and was lower in the 7.5 mg and 5 mg MD groups (79%-83% and 64%-67%, respectively). Prasugrel was well tolerated in healthy Chinese subjects for single doses up to 60 mg and a MD of 10 mg for 10 d. Conclusion: The PKs and PDs of the active metabolite of prasugrel were similar to those in Chinese subjects reported by a previous bridging study, which demonstrated that the exposure to the active metabolite in Chinese subjects was higher than in Caucasians.

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Section: Discussioncontrasting

confidence: 49%

Section: Acta Pharmacologica Sinica Npgmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

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Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects

et al. 2012

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“…38 The higher exposure of the prasugrel active metabolite in East Asian individuals than in white patients translates into the pharmacodynamic profile. [36][37][38][39][40][41][42] In a single-centre study of healthy volunteers, the level of inhibition of platelet aggregation induced by 20 μmol/l ADP in East Asian individuals taking 5 mg of prasugrel daily did not differ from that in white individuals taking 10 mg of p rasugrel daily (mean value at 4 h last-dose: 68.9% vs 70.1%). 40 In Japanese patients undergoing PCI, 15 mg loading and 3.75 mg maintenance doses of prasugrel achieved a faster, higher, and more-consistent antiplatelet effect than 300 mg loading and 75 mg maintenance doses of clopidogrel.…”

Section: P2y 12 Inhibitors In East Asian Patientsmentioning

confidence: 87%

“…In individual studies, the level of the prasugrel active metabolite was 30-47% higher in East Asian patients than in white patients after loading and maintenance doses. [36][37][38][39][40] After adjusting for body mass, active metabolite exposure was still 19% higher in East Asian patients than in white patients, 40 and this finding was more prominent (45-56% higher) in patients with a low body mass (<60 kg). 38 The higher exposure of the prasugrel active metabolite in East Asian individuals than in white patients translates into the pharmacodynamic profile.…”

Section: P2y 12 Inhibitors In East Asian Patientsmentioning

confidence: 95%

World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI

et al. 2014

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| Guideline recommendations on the use of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention (PCI) have been formulated by both the ACC/AHA and the ESC. These recommendations are based primarily on large, phase III, randomized, controlled trials of the P2Y 12 inhibitors clopidogrel, prasugrel, and ticagrelor. However, few East Asian patients have been included in the trials to assess the use of these agents, particularly the newer agents prasugrel and ticagrelor. Additionally, an increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with white patients, and that a different 'therapeutic window' of on-treatment platelet reactivity might be appropriate in East Asian patients. Furthermore, a phenomenon referred to as the 'East Asian paradox' has been described, in which East Asian patients have a similar or even a lower rate of ischaemic events after PCI compared with white patients, despite a higher level of platelet reactivity during DAPT. Recognizing these concerns, the World Heart Federation has undertaken this evidence-based review and produced this expert consensus statement to determine the antiplatelet treatment strategies that are most appropriate for East Asian patients.

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Platelet Aggregation Inhibitory Effects and Pharmacokinetics of Prasugrel Used in Combination With Aspirin in Healthy Japanese Subjects

Umemura

Ikeda

Matsushima

et al. 2016

Clinical Pharm in Drug Dev

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We evaluated the pharmacokinetics and pharmacodynamics of prasugrel used in combination with aspirin in healthy Japanese subjects. All subjects received aspirin 100 mg/day. Subsequently, in the single‐administration study, 23 subjects also received prasugrel 20 or 30 mg, and in the multiple‐administration study, 20 subjects received a loading dose of prasugrel 20 or 30 mg on day 1, followed by a maintenance dose of prasugrel 5 or 7.5 mg/day, respectively, on days 2–5. In both studies, the plasma concentration of the active metabolite of prasugrel, R‐138727, reached a maximum 0.5 hours after administration and rapidly decreased within 4 hours. In the single‐administration study, the inhibitory effect on adenosine diphosphate–induced platelet aggregation was significantly higher in the prasugrel 20‐ and 30‐mg groups than in the placebo group at all times (1–144 hours) after administration. In the multiple‐administration study, a similar antiplatelet effect was found after both the loading dose and the maintenance dose and was maintained for 3–6 days after the last administration. There were study drug‐related adverse events; however, all were mild, and none was clinically significant.

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Pharmacodynamics and pharmacokinetics of single doses of prasugrel 30 mg and clopidogrel 300 mg in healthy chinese and white volunteers: An open-label trial

Cited by 45 publications

References 16 publications

Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects

Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects

World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI

Platelet Aggregation Inhibitory Effects and Pharmacokinetics of Prasugrel Used in Combination With Aspirin in Healthy Japanese Subjects

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