Plasma pharmacokinetics of a liver-selective nitric oxide-donating diazeniumdiolate in the male C57BL/6 mouse

Xenobiotica. 2002 Apr;32(4):339-47. doi: 10.1080/00498250110102665.

Abstract

1. The single-dose plasma pharmacokinetics of O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO) following intravenous (i.v.) and intraperitoneal (i.p.) bolus administration to the male C57BL/6 mouse was studied in an effort to characterize the disposition of the agent and to serve as a basis for the design of in vivo efficacy studies. 2. Plasma V-PYRRO/NO concentrations declined rapidly in a bi-exponential manner after i.v. administration of 5 mg kg(-1) body weight to mouse. The terminal half-life was 9.4 min and the mean residence time was 3.4 min. 3. V-PYRRO/NO was absorbed rapidly following i.p. administration, with peak plasma concentrations being observed 3 min after injection. Levels then declined with a terminal half-life of 11.7 min. The bioavailable fraction from the i.p. compartment was 19%, indicating a high first-pass effect. 4. The results provide additional evidence for a liver-selective metabolism of this nitric oxide-donating prodrug.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Azo Compounds / blood*
  • Azo Compounds / pharmacokinetics*
  • Infusions, Intravenous
  • Injections, Intravenous
  • Liver / blood supply*
  • Liver / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism*
  • Pyrrolidines / administration & dosage

Substances

  • Azo Compounds
  • O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
  • Pyrrolidines
  • diazeniumdiolate
  • Nitric Oxide