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« Previous AbstractSensomics analysis of key hazelnut odorants (Corylus avellana L. 'Tonda Gentile') using comprehensive two-dimensional gas chromatography in combination with time-of-flight mass spectrometry (GCxGC-TOF-MS)    Next AbstractRelationship between pharmacokinetics and hemodynamic effects of inhaled isobutyl nitrite in conscious rats »

Drug Metab Dispos


Title:Pharmacokinetics of a model organic nitrite inhalant and its alcohol metabolite in rats
Author(s):Kielbasa W; Fung HL;
Address:"Department of Pharmaceutics, School of Pharmacy, University at Buffalo, State University of New York, Buffalo, New York 14260, USA"
Journal Title:Drug Metab Dispos
Year:2000
Volume:28
Issue:4
Page Number:386 - 391
DOI:
ISSN/ISBN:0090-9556 (Print) 0090-9556 (Linking)
Abstract:"Volatile organic nitrites were originally used to relieve the chest pain that is associated with angina pectoris. Today, these inhalants are predominantly used as drugs of abuse. Little is known regarding the bioavailability and disposition of volatile nitrites. In this study, the pharmacokinetics of a major organic nitrite inhalant, isobutyl nitrite (ISBN), and its primary metabolite, isobutyl alcohol (ISBA), were investigated after inhalation and i.v. administration. ISBN blood concentrations in the rat declined mono-exponentially with a half-life of 1.4 min and a blood clearance of 2.9 l/min/kg that vastly exceeded cardiac output (0.3 l/min/kg). Approximately 98% of ISBN was metabolized to ISBA, which declined monoexponentially with a half-life of 5.3 min when the infusion of ISBN was terminated. The bioavailability of inhaled ISBN, over a range of 300 to 900 ppm, was estimated to be 43%. After inhaled ISBN, the half-life of ISBA decreased approximately 4-fold (t(1/2) inh = 1.5 min versus t(1/2) i.v. = 5.3 min; P <.001), whereas no pharmacokinetic difference was observed for ISBN. Inhalation of another nitrite, isoamyl nitrite, accelerated the apparent clearance of ISBA, suggesting that nitrite inhalation could change the disposition of another compound. A pharmacokinetic model was developed to describe the concentration-time profile of ISBA and ISBN after inhalation and i.v. administration"
Keywords:"Administration, Inhalation Alcohols/blood/*metabolism Animals Biotransformation Cardiac Output/drug effects Half-Life Infusions, Intravenous Male Nitrites/administration & dosage/blood/*pharmacokinetics Rats Rats, Sprague-Dawley Vasodilator Agents/adminis;"
Notes:"MedlineKielbasa, W Fung, H L eng HL22273/HL/NHLBI NIH HHS/ Research Support, U.S. Gov't, P.H.S. 2000/03/22 Drug Metab Dispos. 2000 Apr; 28(4):386-91"

 
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