title: Time-dependent induction of midazolam-1-hydroxylation enzymes in rats treated with St. John's wort.
abstract: Time-dependent effects of St. John's wort (SJW) on midazolam 1-hydroxylation were investigated in Wistar rats. Wistar rats treated with SJW (1000 mg/kg/d) for 1, 3, and 7 d were administered midazolam orally at a dose of 10 mg/kg. Oral clearance of midazolam in the SJW treated rats increased time dependently, and was significant after 7 d of treatment with SJW. The midazoram-1-hydroxylation activity in liver microsomes obtained from the SJW treated rats was significantly higher than in the control group. Linear correlation was observed between oral clearance and midazolam-1-hydroxylation activity in the liver microsomes, suggesting that CYP3A induction in liver mainly decreased the midazolam concentration in plasma. Immunoblotting revealed that the protein amount of CYP3A was induced within 3 d of SJW treatment. Since the midazolam-1-hydroxylation activity continuously increased for at least 7 d, the induction of CYP3A by SJW continued to cause interactions with drugs metabolized by CYP3A. It is important for persons receiving SJW for an extended time to consider its interactions with prescription drugs.
authors.affiliation: Department of Clinical Pharmacology, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi 371-8511, Japan.
authors.forename: Jing Wei
authors.initials: JW
authors.lastname: Qi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Nakamura
authors.forename: Shin
authors.initials: S
authors.lastname: Hosokawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okada
authors.forename: Ryuya
authors.initials: R
authors.lastname: Horiuchi
authors.forename: Koujirou
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004790:Enzyme Induction; D006900:Hydroxylation; D020902:Hypericum; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008874:Midazolam / Q000378:metabolism* / Q000493:pharmacokinetics; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006899:Mixed Function Oxygenases; D008874:Midazolam