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Imipramine: A model substance in pharmacokinetic research
Author(s) -
Gram Lars F.
Publication year - 1988
Publication title -
acta psychiatrica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.849
H-Index - 146
eISSN - 1600-0447
pISSN - 0001-690X
DOI - 10.1111/j.1600-0447.1988.tb08572.x
Subject(s) - imipramine , desipramine , pharmacokinetics , pharmacology , volume of distribution , steady state (chemistry) , hydroxylation , chemistry , cytochrome p450 , population , metabolism , endocrinology , medicine , biochemistry , enzyme , alternative medicine , environmental health , pathology , hippocampus , antidepressant
The pharmacokinetics of imipramine have been studied over a period of 20 years. Imipramine is rapidly and almost completely metabolized with the formation of desipramine (desmethylation), 2‐hydroxy metabolites and subsequent glucoronide coupling. Imipramine has a high clearance (0.8‐1.5 1/min) and a corresponding high first pass eliminatin (30‐70%). Volume of distribution is high (650‐1100 1) and half‐lives accordingly of medium length (6‐12 h). The 2‐hydroxylation which is the most important step of elimination is mediated via a microsomal cytochrome P450 isozyme that exhibit monogenetic polymorphism such that 5‐10% of the population have a severely reduced clearance. Co‐administration of neuroleptics may also considerably impair the 2‐hydroxylation. Steady‐state levels of imipramine and desipramine varies considerably among individuals mainly due to variations in metabolism, but also to a smaller extent due to variations in binding to plasma proteins. The variations in steady‐state concentrations appear to have clear implication for the clinical effects of imipramine.