Plasma pharmacokinetics of a liver-selective nitric oxide-donating diazeniumdiolate in the male C57BL/6 mouse
- 1 January 2002
- journal article
- research article
- Published by Taylor & Francis in Xenobiotica
- Vol. 32 (4) , 339-347
- https://doi.org/10.1080/00498250110102665
Abstract
1. The single-dose plasma pharmacokinetics of O2-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.Keywords
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