Heading
Abstract
Objective. Little information on the population pharmacokinetics of the tricyclic antidepressant doxepine and its pharmacologically active metabolite desmethyldoxepine is available. However, a more individualised drug therapy may be feasible if the influence of various patient characteristics on plasma concentration was known.
Patients and methods. We retrospectively analysed pharmacokinetic therapeutic drug-monitoring data in 114 psychiatric patients (79 females, 35 males) treated with doxepine for a period of 22–306 days, mostly due to major depression. The data were analysed using the computer program NONMEM. For both, doxepine and its metabolite desmethyldoxepine, a one-compartment model was chosen. Pharmacokinetic parameters clearance (CL/F) and volume of distribution (V/F) of doxepine and desmethyldoxepine were modelled in terms of both random and fixed effects.
Results. The fit of the model to the concentration–time data was significantly improved when V/F was expressed as a function of weight (P<0.05) and CL/F as a function of age (P<0.05). Co-medication that inhibits P 450 isoenzymes lowered CL/F of doxepine by 15%.
Conclusion. The analysis indicates that the factors age and, to some extent, body weight may be a guidance for individual doxepine dose regimens, which however needs confirmation in prospective clinical trials linking pharmacokinetics and therapeutic effect. Co-medication may represent only a minor important covariate.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Accepted in revised form: 18 February 2002
Electronic Publication
Rights and permissions
About this article
Cite this article
Meyer-Barner, M., Meineke, I., Schreeb, K. et al. Pharmacokinetics of doxepin and desmethyldoxepin: an evaluation with the population approach. Eur J Clin Pharmacol 58, 253–257 (2002). https://doi.org/10.1007/s00228-002-0448-3
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-002-0448-3