Model for the kinetics of imipramine and its metabolites in adolescents.

Abstract

A kinetic model for imipramine (IMI) has been developed, based upon a study of 16 teenagers who received IMI 4-5 mg/kg/day for treatment of a major depressive disorder. Serial measurements of plasma concentrations of IMI, desmethylimipramine (DMI), 2-hydroxy-IMI, and 2-hydroxy-DMI were made. Mean residence times, volumes of distribution, clearances of IMI and DMI, and rate constants for formation and elimination of the hydroxy metabolites were determined from a multicompartment model fitted to the concentration-time data. Mean residence time for DMI was significantly longer than for IMI (47.1 +/- 21.2 vs. 13.4 +/- 4.8 h, p less than 0.001). A different volume of distribution for IMI and DMI was not supported by the data. Clearance of DMI was considerably slower than that of IMI (0.67 +/- 0.45 vs. 2.18 +/- 1.33 l(kg.h), p less than 0.001). A statistically significant increase in mean residence time with increasing age during adolescence was found (r = 0.57, p less than 0.05).

• Authors: R B Dell, K Hein, R Ramakrishnan, J Puig-Antich, T Cooper
• Journal: Therapeutic drug monitoring (Ther Drug Monit) Vol. 12 Issue 5 Pg. 450-9 (Sep 1990) ISSN: 0163-4356 [Print] United States
• PMID: 2293407 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 2-hydroxyimipramine
• Imipramine
• Desipramine
• 2-hydroxydesipramine

Topics

• Adolescent
• Desipramine (analogs & derivatives, blood, pharmacokinetics)
• Female
• Humans
• Imipramine (analogs & derivatives, blood, pharmacokinetics, therapeutic use)
• Male
• Models, Biological
• Models, Theoretical