Comparison of single dose kinetics of imipramine, nortriptyline and antipyrine in man

The single dose kinetics of imipramine (IP), nortriptyline (NT), and antipyrine (AP) were compared in 7 healthy subjects. Test doses of AP were given intravenously and test doses of IP and NT were given both orally and by intravenous infusion. The plasma concentration/time curves after intravenous I...

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Bibliographic Details
Published in:Psychopharmacology 1976-01, Vol.50 (1), p.21-27
Main Authors: Gram, L F, Andreasen, P B, Overo, K F, Christiansen, J
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Antipyrine - blood
Antipyrine - metabolism
Female
Half-Life
Humans
Imipramine - administration & dosage
Imipramine - blood
Imipramine - metabolism
Infusions, Parenteral
Kinetics
Liver Circulation
Male
Models, Biological
Nortriptyline - administration & dosage
Nortriptyline - blood
Nortriptyline - metabolism
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Summary:The single dose kinetics of imipramine (IP), nortriptyline (NT), and antipyrine (AP) were compared in 7 healthy subjects. Test doses of AP were given intravenously and test doses of IP and NT were given both orally and by intravenous infusion. The plasma concentration/time curves after intravenous IP and NT were analysed according to a 2-compartment open model. In addition a blood flow independent 'true' clearance was calculated according to a sinusoidal perfusion model. Indirect estimates of hepatic blood flow were obtained from the oral and i.v. plasma concentration/time curves after NT administration. Compared to NT, IP had statistically significant higher clearances, shorter half-lives, and smaller apparent volumes of distribution. There was a significant correlation between apparent volume of distribution (Vdbeta) of IP and NT (n = 5, r = 0.85), but only a weak correlation between the clearance measurements of the two compounds. Systemic clearance of AP and IP showed some positive correlation (n = 7, r = 0.73), whereas there were no significant correlations between AP and NT kinetics. The data indicate that inter- and intraindividual variations in hepatic blood flow may influence the measurements. Other possible sources of variability are individual differences in hepatic extraction kinetics, and differences in binding to blood constituents.
ISSN:0033-3158
1432-2072
DOI:10.1007/bf00634149