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Nonlinear Kinetics of Trimipramine in Depressed Patients
Author(s) -
Musa Mahmoud N.
Publication year - 1989
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1989.tb03410.x
Subject(s) - nortriptyline , desipramine , tricyclic , metabolite , pharmacokinetics , chemistry , imipramine , hydroxylation , pharmacology , active metabolite , plasma concentration , kinetics , cyp2d6 , chromatography , metabolism , medicine , cytochrome p450 , amitriptyline , biochemistry , enzyme , physics , alternative medicine , pathology , quantum mechanics , hippocampus , antidepressant
An increase of the dose of trimipramine (TM) results in a markedly disproportionate increase of the steady‐state plasma concentration of the major active metabolite desmethyltrimipramine (DMT). Ten patients receiving 75 mg/day of TM had a mean steady‐state plasma concentration of 53.8 ng/ml TM and 26.3 ng/ml DMT. Ten others receiving 150 ng/ml TM had a mean concentration of 122.5 ng/ml TM and 133.8 ng/ml DMT. This is most likely due to the saturation within therapeutic dosage range of the subspecies of cytochrome P‐450 responsible for hydroxylation of DMT. Available data on metabolism of tricyclic antidepressants shows that the hydroxylation of desmethylimipramine (desipramine) but not that of desmethylamitriptyline (nortriptyline) reaches saturation within therapeutic dosage range. Clinicians should take into consideration the possibility of dose‐dependent kinetics when adjusting the dose of tricyclic antidepressants. This ending highlights the value of monitoring of blood levels of antidepressants.