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

Abstract

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.