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Pharmacokinetic interaction between nortriptyline and terbinafine. 2002

P-Hugo M Van Der Kuy, and Harrie A Van Den Heuvel, and Rob W Kempen, and Leo M L Vanmolkot
Department of Clinical Pharmacy and Toxicology, Academic Hospital Maastricht, Netherlands. hkuy@kfls.azm.nl

OBJECTIVE To clarify the mechanism of interaction between nortriptyline and terbinafine. METHODS Nortriptyline intoxication secondary to terbinafine treatment was observed in a woman with a major depressive disorder. This is the second report of this interaction. A rechallenge was performed during which serum concentrations were measured of nortriptyline and the 2 hydroxy metabolites. To document the case, genotyping of CYP2D6 was also performed. CONCLUSIONS Metabolism by CYP2D6 is of major importance for the hydroxylation of nortriptyline, making it susceptible to competitive inhibition by terbinafine. CONCLUSIONS The pharmacokinetic interaction between nortriptyline and terbinafine is probably due to inhibition of CYP2D6 of the nortriptyline metabolism by terbinafine. The interaction is not restricted to a subpopulation, but may occur even in persons without deviations in CYP2D6.

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009281 Naphthalenes Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
D009661 Nortriptyline A metabolite of AMITRIPTYLINE that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. Desitriptyline,Desmethylamitriptylin,Allegron,Apo-Nortriptyline,Aventyl,Gen-Nortriptyline,Norfenazin,Nortrilen,Nortriptyline Hydrochloride,Novo-Nortriptyline,Nu-Nortriptyline,PMS-Nortriptyline,Pamelor,Paxtibi,ratio-Nortriptyline,Apo Nortriptyline,Gen Nortriptyline,Hydrochloride, Nortriptyline,Novo Nortriptyline,Nu Nortriptyline,PMS Nortriptyline,ratio Nortriptyline
D003866 Depressive Disorder An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. Depression, Endogenous,Depression, Neurotic,Depression, Unipolar,Depressive Syndrome,Melancholia,Neurosis, Depressive,Unipolar Depression,Depressions, Endogenous,Depressions, Neurotic,Depressions, Unipolar,Depressive Disorders,Depressive Neuroses,Depressive Neurosis,Depressive Syndromes,Disorder, Depressive,Disorders, Depressive,Endogenous Depression,Endogenous Depressions,Melancholias,Neuroses, Depressive,Neurotic Depression,Neurotic Depressions,Syndrome, Depressive,Syndromes, Depressive,Unipolar Depressions
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077291 Terbinafine A naphthalene derivative that inhibits fungal SQUALENE EPOXIDASE and is used to treat DERMATOMYCOSES of the skin and nails. (E)-N-(6,6-Dimethyl-2-heptenynyl)-N-methyl-1-naphthalenementhamin hydrochloride,DA 5505,Lamisil,SF 86-327,SF-86-327,TDT-067,Terbinafine Hydrochloride,Terbinafine, (Z)-,Terbinafine, (Z)-isomer,SF 86 327,SF 86327,SF86327,TDT 067,TDT067
D000929 Antidepressive Agents, Tricyclic Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However, the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system. Antidepressants, Tricyclic,Tricyclic Antidepressant,Tricyclic Antidepressant Drug,Tricyclic Antidepressive Agent,Tricyclic Antidepressive Agents,Antidepressant Drugs, Tricyclic,Agent, Tricyclic Antidepressive,Agents, Tricyclic Antidepressive,Antidepressant Drug, Tricyclic,Antidepressant, Tricyclic,Antidepressive Agent, Tricyclic,Drug, Tricyclic Antidepressant,Drugs, Tricyclic Antidepressant,Tricyclic Antidepressant Drugs,Tricyclic Antidepressants

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