skip to main content
Ngôn ngữ:
Giới hạn tìm kiếm: Giới hạn tìm kiếm: Dạng tài nguyên Hiển thị kết quả với: Hiển thị kết quả với: Chỉ mục

Nonlinear Pharmacokinetics of 5-Methoxy-N,N-dimethyltryptamine in Mice

Shen, H.-W. ; Jiang, X.-L. ; Yu, A.-M.

Drug Metabolism and Disposition, 07/01/2011, Vol.39(7), pp.1227-1234 [Tạp chí có phản biện]

E-ISSN: 1521-009X ; DOI: http://dx.doi.org/10.1124/dmd.111.039107

Toàn văn sẵn có

Trích dẫn Trích dẫn bởi
  • Nhan đề:
    Nonlinear Pharmacokinetics of 5-Methoxy-N,N-dimethyltryptamine in Mice
  • Tác giả: Shen, H.-W. ; Jiang, X.-L. ; Yu, A.-M.
  • Chủ đề: Pharmacy, Therapeutics, & Pharmacology
  • Là 1 phần của: Drug Metabolism and Disposition, 07/01/2011, Vol.39(7), pp.1227-1234
  • Mô tả: 5-Methoxy-N,N,-dimethyltryptamine (5-MeO-DMT), an abused serotonergic indolealkylamine drug, was placed into Schedule I controlled substance status in the United States as of January 19, 2011. In previous studies, we have shown the impact of monoamine oxidase A and cytochrome P450 2D6 enzymes on 5-MeO-DMT metabolism and pharmacokinetics. The aim of this study was to investigate 5-MeO-DMT pharmacokinetic properties after intravenous or intraperitoneal administration of three different doses (2, 10, and 20 mg/kg) to CYP2D6-humanized (Tg-CYP2D6) and wild-type control mice. Systemic exposure [area under the curve (AUC)] to 5-MeO-DMT was increased nonproportionally with the increase in dose. The existence of nonlinearity in serum 5-MeO-DMT pharmacokinetics was clearly manifested by dose-normalized AUC values, which were approximately 1.5- to 2.0-fold (intravenous) and 1.8- to 2.7-fold (intraperitoneal) higher in wild-type or Tg-CYP2D6 mice dosed with 10 and 20 mg/kg 5-MeO-DMT, respectively, than those in mice treated with 2 mg/kg 5-MeO-DMT. Furthermore, a two-compartment model including first-order absorption, nonlinear (Michaelis-Menten) elimination, and CYP2D6-dependent linear elimination from the central compartment was developed to characterize the intravenous and intraperitoneal pharmacokinetic data for 5-MeO-DMT in wild-type and Tg-CYP2D6 mice. In addition, 5-MeO-DMT was readily detected in mouse brain after drug treatment, and brain 5-MeO-DMT concentrations were also increased nonproportionally with the increase of dose. The results establish a nonlinear pharmacokinetic property for 5-MeO-DMT in mice, suggesting that the risk of 5-MeO-DMT intoxication may be increased nonproportionally at higher doses.
  • Ngôn ngữ: English
  • Số nhận dạng: E-ISSN: 1521-009X ; DOI: http://dx.doi.org/10.1124/dmd.111.039107

Đang tìm Cơ sở dữ liệu bên ngoài...