title: Effects of single or repeated silymarin administration on pharmacokinetics of risperidone and its major metabolite, 9-hydroxyrisperidone in rats.
abstract: 1. The interactions between herbal dietary supplements and therapeutic drugs have emerged as an important issue and P-glycoprotein (P-gp) has been reported as one of the significant factors of these interactions.   2. The objective of this article is to examine the effects of single and repeated administrations of silymarin on pharmacokinetics of a P-gp substrate, risperidone, and its major metabolite, 9-hydroxyrisperidone, in rats.   3. To determine the plasma levels of risperidone and 9-hydroxyrisperidone in rats, a HPLC method was developed using a liquid-liquid acid back extraction. When risperidone (6 mg/kg) was co-administered with silymarin (40 mg/kg) to rats orally, the C(max) of 9-hydroxyrisperidone was significantly increased to1.3-fold (p < 0.05), while the other pharmacokinetic parameters did not show any significant differences. Expanding the experiment where rats were repeatedly administered with silymarin for 5 days prior to giving risperidone, the C(max) of risperidone and 9-hydroxyrisperidone were significantly increased to 2.4-fold (p < 0.001) and 1.7-fold (p < 0.001), respectively, and the AUC(0-t), as well to 1.7-fold (p < 0.05) and 2.1-fold (p < 0.01), respectively.   4. The repeated exposures of silymarin, compared to single administration of silymarin, increased oral bioavailability and affected the pharmacokinetics of risperidone and 9-hydroxyrisperidone, by inhibiting P-gp.
authors.affiliation: Center for Cell Signaling & Drug Discovery Research, Division of Life and Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: Kyoung Sin
authors.initials: KS
authors.lastname: Lee
authors.forename: Song Wha
authors.initials: SW
authors.lastname: Chae
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Choi
authors.forename: Sandy Jeong Yeon
authors.initials: SJ
authors.lastname: Rhie
authors.forename: Hwa Jeong
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007555:Isoxazoles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D012838:Silymarin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D007555:Isoxazoles; D011743:Pyrimidines; D012838:Silymarin; D018967:Risperidone; D000068882:Paliperidone Palmitate