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 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.
D000284:Administration, Oral; D000328:Adult; D000983:Antipyrine / Q000097:blood / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007099:Imipramine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007263:Infusions, Parenteral; D007700:Kinetics; D008102:Liver Circulation; D008297:Male; D008954:Models, Biological; D009661:Nortriptyline / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D009661:Nortriptyline; D007099:Imipramine; D000983:Antipyrine