The pharmacokinetics and pharmacodynamics of prasugrel in healthy Chinese, Japanese, and Korean subjects compared with healthy Caucasian subjects

Small, David S.; Kothare, Prajakti A.; Yuen, Eunice; Lachno, D. Richard; Li, Ying G.; Winters, Kenneth J.; Farid, Nagy A.; Ni, Lan; Jakubowski, Joseph A.; Salazar, Daniel E.; Thieu, Vivian T.; Payne, Christopher D.

doi:10.1007/s00228-009-0737-1

Cited by 63 publications

(61 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was reported that in healthy European subjects, prasugrel at a dose of 60 mg showed about 80% platelet aggregation inhibition, which was almost the same as that in Japanese subjects receiving 20 mg prasugrel 19. This might be related to the plasma concentration of the active metabolite of prasugrel in Asian groups being found to be higher than that in white groups 20. The lower mean body weight of Asian subjects compared with white subjects may contribute to the higher concentration of the active metabolite in Asians.…”

Section: Discussionmentioning

confidence: 91%

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

Umemura

Iwaki

2016

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

The dosing regimen of prasugrel adjusted for Japanese patients was compared with that of clopidogrel by analyzing the pharmacokinetics and pharmacodynamics in 40 healthy Japanese subjects in a randomized, single‐blind crossover study. In period 1, the subjects received either 300 mg clopidogrel or 20 mg prasugrel; after a >2‐week interval (period 2), the drug was switched. Blood samples of 36 of the 40 subjects were collected for analysis of pharmacokinetics, pharmacodynamics, and CYP2C19 genotypes. The plasma concentration of the active metabolite of prasugrel increased rapidly and reached its peak 30 minutes postadministration, whereas that of the active metabolite of clopidogrel reached its peak 1 hour postadministration. The mean AUC and Cmax of the active metabolite of clopidogrel, but not those of prasugrel, were CYP2C19 genotype dependent. Prasugrel rapidly inhibited platelet aggregation, reaching its maximum effect 1 hour postadministration. Clopidogrel, on the other hand, showed maximum inhibition 2 hours postadministration. Platelet aggregation inhibition by clopidogrel was significantly lower in the poor‐metabolizer subjects than in the extensive‐metabolizer subjects. Overall, prasugrel inhibited platelet aggregation more rapidly and more effectively in healthy Japanese subjects than was observed for clopidogrel.

show abstract

Section: Discussionmentioning

confidence: 91%

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

Umemura

Iwaki

2016

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

show abstract

“…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: 87%

“…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%

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

et al. 2012

View full text Add to dashboard Cite

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.

show abstract

“…[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. 41 Likewise, the exposure of ticagrelor and its major active metabolite (AR-C124910XX) was higher in East Asian individuals than in white individuals after loading and maintenance doses.…”

Section: P2y 12 Inhibitors In East Asian Patientsmentioning

confidence: 88%

“…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: 98%

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

et al. 2014

View full text Add to dashboard Cite

| 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.

show abstract

The pharmacokinetics and pharmacodynamics of prasugrel in healthy Chinese, Japanese, and Korean subjects compared with healthy Caucasian subjects

Abstract: Mean exposure to the prasugrel active metabolite following prasugrel 60-mg LD and during daily 10-mg or 5-mg MD was higher in each of the Asian groups than in the Caucasian group, which resulted in greater platelet inhibition.

Cited by 63 publications

References 11 publications

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

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

Contact Info

Product

Resources

About