Dose-dependent pharmacokinetics of the antihypertensive 2,3,4,4a-tetrahydro-1H-pyrazino[1,2a]quinoxalin-5-(6H)-one in dogs and rats
A sensitive and reproducible GLC assay was developed for determining 2,3,4,4a-tetrahydro-1H-pyrazino[1,2a]quinoxalin-5(6H)-one (I) in biological fluids, utilizing the electron-capturing capability of the heptafluorobutyryl derivative. After single 2.5- and 10-mg/kg oral and intravenous doses to thre...
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Published in | Journal of pharmaceutical sciences Vol. 71; no. 4; p. 414 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
01.04.1982
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Subjects | |
Online Access | Get more information |
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Summary: | A sensitive and reproducible GLC assay was developed for determining 2,3,4,4a-tetrahydro-1H-pyrazino[1,2a]quinoxalin-5(6H)-one (I) in biological fluids, utilizing the electron-capturing capability of the heptafluorobutyryl derivative. After single 2.5- and 10-mg/kg oral and intravenous doses to three dogs, plasma concentration-time data for I were fitted to a biexponential equation and pharmacokinetic parameters were calculated. A dose-dependency for certain parameters, most notably total body clearance (ClT), was indicated. The difference in ClT for the low and high dose was statistically significant. After single 5-, 25-, and 50-mg/kg intragastric doses were given to rats, the decline in plasma concentrations of I with time followed a monoexponential equation. As with dogs, there was a disproportionate change in kinetic parameters with increasing dose for rats. While simple Michaelis-Menten kinetics were not evident, nonlinearity in biotransformation (intrinsic clearance) appeared to be the cause for the dose-dependent pharmacokinetics. |
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ISSN: | 0022-3549 |
DOI: | 10.1002/jps.2600710410 |