Preclinical study of a potent P-glycoprotein and cytochrome P450 enzyme inducer rifampicin changing pharmacokinetic parameters of risperidone and its metabolite, 9-hydroxyrisperidone, using a rat model
- 주제(키워드) 9-Hydroxyrisperidone , Bioavailability , Drug interactions , P-Glycoprotein , Rifampicin , Risperidone
- 등재 KCI등재, SCOPUS
- 발행기관 The Korean Society of Pharmaceutical Sciences and Technology
- 발행년도 2012
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000096788
- 본문언어 영어
- Published As http://dx.doi.org/10.1007/s40005-012-0045-0
초록/요약
The objective of the present investigation is to examine the effects of rifampicin, which is a P-glycoprotein (P-gp) and cytochrome P450 (CYP)3A4 inducer, on the pharmacokinetics of risperidone and its active metabolite, 9-hydroxyrisperidone, in rats. To determine the plasma levels of risperidone and 9-hydroxyrisperidone in rats, a high performance liquid chromatographic method was developed using a liquid-liquid acid back extraction. After pretreated with rifampicin (600 mg/kg) for 6 days, the mean Cmax and AUC0-10 values of risperidone were significantly decreased and the Clt of the drug was significantly increased compared with control (p < 0.01, <0.05, and <0.05, respectively). The Cmax and AUC0-424 of 9-hydroxyrisperidone were also significantly decreased compared with control (p < 0.01, respectively). Thus, the relative bioavailability of risperidone and 9-hydroxyrisperidone once pretreated with rifampicin (600 mg/kg) was 42.5 and 32.5 %, respectively. The exposure of rifampicin significantly decreased oral bioavailability and affected the pharmacokinetics of risperidone and its active metabolite, 9-hydroxyrisperidone, by the induction of P-gp and CYP3A4 as well.
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