The Influence of Smoking on the Serum Level of Duloxetine

Abstract

Duloxetine is a dual acting antidepressant (selective serotonin and norepinephrine reuptake inhibitor). Existing data suggest that the advisable therapeutic serum level of duloxetine ranges between 20 and 80 ng/mL. In a naturalistic setting we determined duloxetine serum levels within a steady state in a sample of depressive inpatients by high performance liquid chromatography (HPLC). The mean serum levels in 28 patients at the time of the first TDM analysis were 52.0±67 ng/mL. Eight of the patients were smokers and showed a considerably lower serum level of 24.3±18.8 ng/mL. In the further course of treatment the difference was compensated by application of higher doses in smokers. These findings suggest that smoking is associated with lower duloxetine serum levels due to an induction of CYP1A2 by polycylic hydrocarbons which are contained in tobacco smoke. Therefore in smokers higher doses of duloxetine (about 15%) seem to be necessary to reach adequate serum levels.

References

• 1 Arnold LM, Lu Y, Crofford LJ, Wohlreich M, Detke MJ, Iyengar S, Goldstein DJ. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder.  Arthritis Rheum. 2004;  50 2974-2984
• 2 Bauer M, Whybrow PC, Angst J, Versiani M, Möller H-J. Biologische Behandlung unipolarer depressiver Störungen. Behandlungsleitlinien der World Federation of Societies of Biological Psychiatry (WFSBP). Wissenschaftliche Verlagsgesellschaft mbH Stuttgart 2004
• 3 Brosen K. Some aspects of genetic polymorphism in the biotransformation of antidepressants.  Therapie. 2004;  59 5-12
• 4 Dalack GN, Glassman AH, Rivelli S, Covey L, Stetner F. Mood, major depression, and fluoxetine response in cigarette smokers.  Am J Psychiatry. 1995;  152 398-403
• 5 DeLeon J, Becona E, Gurpegui M. et al . The association between high nicotine dependence and severe mental illness may across countries.  J Clin Psychiat. 2002;  63 812-816
• 6 Detke MJ, Lu Y, Goldstein DJ, Hayes JR. et al . Duloxetine, 60 mg once daily, for major depressive disorder: A randomized double-bilnd placebo-controlled trial.  J Clin Psychiat. 2002;  63 308-315
• 7 Detke MJ, Lu Y, Goldstein DJ, MacNamara RK, Demitrack MA. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression.  J Psychiatr Res. 2002;  36 383-390
• 8 Dunner DL, Goldstein DJ, Mallinckrodt C, Lu , Detke MJ. Duloxetine in treatment of anxiety symptoms associated with depression.  Depress Anxiety. 2003;  18 53-61
• 9 EMEA . European Public Assessment of Medical Products. Scientific discussion. Cymbalta 2005
• 10 Faber MS, Fuhr U. Time response of cytochrome P450 1A2 activity on cessation of heavy smoking.  Clin Pharmacol Ther. 2004;  76 178-184
• 11 Faber MS, Jetters A, Fuhr U. Assessment of CYP1A2 activity in clinical practice: Why, how and when?.  Bas Clin Pharmacol Toxicol. 2005;  97 125-134
• 12 George TP, Ziedonis DM, Feingold A, Pepper WT, Satterburg CA, Winkler J. et al . Nicotine transdermal patch and atypical antipsychotic medication for smoking cessation in schizophrenia.  Am J Psychiatry. 2000;  157 1835-1842
• 13 Goldstein DJ, Lu Y, Detke MJ, Wiltse C, Mallinckrodt C, Demittrack MA. Duloxetine in the treatment of depression: a double- blind placebo-controlled comparison with paroxetine.  J Clin Pharmacol. 2004;  24 389-399
• 14 Hiemke C, Hampel C, Weigmann H. Pharmakologie von Duloxetin. Eine therapeutische Option für verschiedene Indikationen.  Psychopharmakotherapie. 2006;  13 12-18
• 15 Ishigooka J, Nagata E, Takahashi A. et al . Simultaneous monitoring of inhibition of serotonin uptake by platelets and plasma drug concentrations following administration of duloxetine, a new antidepressant candidate, to healthy volunteers.  Curr Ther Res. 1997;  58 679-692
• 16 Iyengar S, Bymaster FP, Wong DT, Ahmad L. et al . Efficacy of the selective serotonin and norepinephrine reuptake inhibitor, duloxetine, in the formalin model of persistent pain.  Eur Neuropsychopharmacol. 2002;  12 ((Suppl 13)) 215
• 17 Lantz RJ, Hillespie TA, Rash TJ, Kuo F. et al . Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects.  Drug Metab Dispos. 2003;  31 1142-1150
• 18 Lott RS, Baker DE. Duloxetine:a new antidepressant.  Adv Pharmacy. 2003;  1 228-241
• 19 Millard R, Morre K, Rencken R, Yalcin I. et al . Duloxetine versus placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial.  BJU Int. 2004;  93 311-318
• 20 Müller WE, Haen E, Fritze J. et al . Selektive Serotonin- und Noradrenalin-Wiederaufnahmehemmer (SSNRI). Antidepressiva mit dualem Wirkungsmechanismus.  Psychopharmakotherapie. 2004;  11 71-75
• 21 Nemeroff CB, DeVane CL, Pollock BG. Newer antidepressant and the cytochrome P450 system.  Am J Psychiatry. 1995;  153 311-320
• 22 Salokanga RK, Saarijarvi S, Taiminen T. et al . Effect of smoking on neuroleptics in schizophrenia.  Schizophr Res. 1997;  23 55-60
• 23 Schreiber S, Backer MM, Pick CG. The antinociceptive effect of venlafaxine in mice is mediated through opioid and adrenergic mechanism.  Neurosci Lett. 1999;  173 85-88
• 24 Sharif ZA. Pharmacokinetics, metabolism, and drug drug interactions of atypical antipsychotics in special populations.  Primary care companion J Clin Psychiat. 2003;  64 22-25
• 25 Sharma A, Goldberg MJ, Cerimele BJ. Pharmacokinetics and safety of duloxetine, a dual-serotonin and norepinephrine reuptake inhibitor.  J Clin Pharmacol. 2000;  40 161-167
• 26 Tang Y-I, Mao P, Li F-M, Chen Q, Jiang F, Cai Z-J, Mitchell PB. Gender, age, smoking behaviour and plasma clozapine concentration in 193 Chinese inpatients with schizophrenia.  Br J Clinical Pharmacol, Online Early Articles. 12;  Feb 2007-03-05
• 27 Thor KB, Katofiasc MA. Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neuron control of lower urinary tract function in the chloralose-anesthetized female cat.  J Pharmacol Exp Ther. 1995;  274 1014-1024
• 28 Kerreboreck P Van, Abrams P, Lange R, Slack M. et al . Duloxetine vs. placebo in the treatment of European and Canadian women with stress urinary incontinence.  Br J Obstet Gynaecol. 2004;  111 249-257
• 29 Zagermann-Muncke P. Rauchen gefährdet ihre Arzneimitteltherapie. http://www.pharmazeutische-zeitung.de/fileadmin/pza/2004-29/pharma4.htm , < http://www.pharmazeutische-zeitung.de/fileadmin/pza/2004-29/pharma4.htm
• 30 Ziedonis DM, Kosten TR, Glazer WM. et al . Nicotine dependence and schizophrenia.  Hosp and Comm Psychiat. 1994;  45 204-206
• 31 Ziedonis DM, George TP. Schizophrenia and nicotine use: report of pilot smoking cessation program and review of neurobiological and clinical issues.  Schizophr Bull. 1997;  23 247-254
• 32 Zink M, Knopf U, Mase E, Kuwilsky A, Deuschle M. Duloxetine treatment of major depressive episodes in the course of psychotic disorders.  Pharmacopsychiatry. 2006;  39 109-111
• 33 Zullino DF, Delessert D, Eap CB, Preisig M, Baumann P. Tobacco and cannabis smoking cessation can lead to intoxication with clozapine and olanzapine.  Int Clin Psychopharmacol. 2002;  17 141-143

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