Pharmacokinetics, pharmacodynamics, and tolerability of single and multiple doses of ticagrelor in Japanese and Caucasian volunteers.
Int J Clin Pharmacol Ther
; 52(6): 478-91, 2014 Jun.
Article
en En
| MEDLINE
| ID: mdl-24755129
OBJECTIVES: Two studies assessing ticagrelor pharmacokinetics, pharmacodynamics, and tolerability in healthy Japanese and Caucasian volunteers. MATERIALS AND METHODS: Single-ascending dose (SAD) study: Japanese (n = 20) and Caucasians (n = 20) received single doses of ticagrelor (50, 100, 200, 300, 400, and 600 mg) or placebo. Multiple-ascending dose (MAD) study: Japanese (n = 36) and Caucasians (n = 36) received single doses of 100 mg or 300 mg ticagrelor (day 1), twice-daily 100 mg or 300 mg ticagrelor, or placebo (days 4 â 9), and single doses of 100 mg or 300 mg ticagrelor (day 10). RESULTS: Exposure to ticagrelor and its active metabolite, AR-C124910XX, was generally higher in Japanese vs. Caucasians. In the SAD study, area under the plasma concentration-time curve (AUC) values were 33% (ticagrelor) and 55% (AR-C124910XX) greater in Japanese vs. Caucasians following 600 mg ticagrelor. In the MAD study, AUC values of ticagrelor and AR-C124910XX following multiple doses of ticagrelor 100 mg and 300 mg were statistically significantly greater (33 - 48%) in Japanese vs. Caucasians. In both groups, mean peak inhibition of platelet aggregation was > 86% after single doses (>= 100 mg ticagrelor) and > 84% after multiple doses. Bleeding times were >= 60 minutes in more Japanese than Caucasians with multiple dosing of 100 mg and 300 mg ticagrelor Adverse events were similar between groups (mild-to-moderate intensity). CONCLUSIONS: The pharmacokinetics and tolerability of ticagrelor were broadly similar in Japanese and Caucasians, although exposure was slightly greater in Japanese volunteers. Ticagrelor was generally well tolerated.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Agregación Plaquetaria
/
Adenosina
/
Pueblo Asiatico
/
Población Blanca
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Antagonistas del Receptor Purinérgico P2Y
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
País/Región como asunto:
America do norte
/
Asia
Idioma:
En
Revista:
Int J Clin Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Alemania