Details

Autor(en) / Beteiligte

• Kubo, Masanori
• Koue, Toshiko
• Maune, Hiromi
• Fukuda, Tsuyoshi
• Azuma, Junichi

Titel

Pharmacokinetics of Aripiprazole, a New Antipsychotic, following Oral Dosing in Healthy Adult Japanese Volunteers: Influence of CYP2D6 Polymorphism

Ist Teil von

• DRUG METABOLISM AND PHARMACOKINETICS, 2007-01, Vol.22 (5), p.358-366

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• We investigated the pharmacokinetics (PK) of aripiprazole, a newly developed antipsychotic, and its active metabolite in healthy Japanese, and the influence of CYP2D6 polymorphism on the PK of aripiprazole. Following a single oral 6mg dose, the mean Cmax, tmax, and t1/2,z (terminal phase half life) of aripiprazole were 31.0ng/mL, 3.6hr, and 61.0hr, respectively. The t1/2,z in CYP2D6 IM subjects (75.2hr) was significantly (p<0.01) longer than that in CYP2D6 EM subjects (45.8hr), and the systemic clearance of IM subjects was approximately 60% that of EM subjects. The PK in one subject with the CYP2D6*41 homozygote was similar to that of IM subjects. In repeated oral administration, plasma concentrations of aripiprazole and active metabolite both reached a steady state by Day 14. The half-life of aripiprazole following repeated administration was similar to that following single administration, suggesting that pharmacokinetics was constant during 14-day administration. Our investigations revealed that there is no clear ethnic difference between Japanese and Western subjects in terms of mean plasma PK, while the CYP2D6*10 allele distinctive to Asian populations influences the PK of aripiprazole. Moreover, our observations suggest that the CYP2D6*41 allele significantly affects drug-metabolizing activity.