Duloxetine: Clinical pharmacokinetics and drug interactions

Clinical Pharmacokinetics

Volumn 50, Issue 5, 2011, Pages 281-294

  Knadler, Mary Pat ^a   Lobo, Evelyn ^a   Chappell, Jill ^a   Bergstrom, Richard ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Adrenergic uptake inhibitors, pharmacokinetics; Antidepressants, pharmacokinetics; Drug interactions; Duloxetine, drug interactions; Duloxetine, pharmacokinetics; Liver dysfunction; Renal impairment; Serotonin uptake inhibitors, pharmacokinetics

Indexed keywords

4 HYDROXY DULOXETINE; 5 HYDROXY 6 METHOXY DULOXETINE; ACENOCOUMAROL; ACTIVATED CARBON; AMITRIPTYLINE; ARIPIPRAZOLE; CYTOCHROME P450 1A2; CYTOCHROME P450 2D6; DESIPRAMINE; DULOXETINE; ESCITALOPRAM; FAMOTIDINE; FLECAINIDE; FLUVOXAMINE; IMIPRAMINE; LINEZOLID; LORAZEPAM; METOPROLOL; MOCLOBEMIDE; MYLANTA; NORTRIPTYLINE; PAROXETINE; PROPAFENONE; RISPERIDONE; SEROTONIN NORADRENALIN REUPTAKE INHIBITOR; SERTRALINE; TOLTERODINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; WARFARIN;

AREA UNDER THE CURVE; CONSTIPATION; DEMOGRAPHY; DIALYSIS; DIARRHEA; DIZZINESS; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG EXPOSURE; DRUG INHIBITION; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENTIATION; DRUG TOLERABILITY; ETHNICITY; FATIGUE; FIBROMYALGIA; GENERALIZED ANXIETY DISORDER; GENETIC POLYMORPHISM; GENOTYPE; HEADACHE; HUMAN; HYPERHIDROSIS; IN VITRO STUDY; INSOMNIA; KIDNEY DISEASE; KIDNEY FAILURE; KIDNEY FUNCTION; LACTATION; LIVER DISEASE; LIVER FUNCTION; MAJOR DEPRESSION; NAUSEA; NEUROPATHIC PAIN; NONHUMAN; PLASMA CONCENTRATION-TIME CURVE; PLASMA PROTEIN BINDING; PRIORITY JOURNAL; RESTLESSNESS; REVIEW; SARCOMA; SEROTONIN SYNDROME; SEX DETERMINATION; SINGLE DRUG DOSE; SMOKING; SOMNOLENCE; STOMACH PH; STRESS INCONTINENCE; TIC; TREMOR; XEROSTOMIA;

ADRENERGIC UPTAKE INHIBITORS; ADULT; AGED; ANIMALS; DRUG INTERACTIONS; FEMALE; HUMANS; MALE; MIDDLE AGED; PHARMACOGENETICS; RISK ASSESSMENT; RISK FACTORS; SEROTONIN UPTAKE INHIBITORS; THIOPHENES;

EID: 79953329390     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.2165/11539240-000000000-00000     Document Type: Review

References (68)

1. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology 2001; 25 (6): 871-80. (Pubitemid 34031892)
2. Bymaster FP, Lee TC, Knadler MP, et al. The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. Curr Pharm Des 2005; 11 (12): 1475-93. (Pubitemid 40691447)
3. Turcotte JE, Debonnel G, de MC, et al. Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects. Neuropsychopharmacology 2001; 24 (5): 511-21. (Pubitemid 32244312)
4. Wong DT, Bymaster FP, Mayle DA, et al. LY248686, a new inhibitor of serotonin and norepinephrine uptake. Neuropsychopharmacology 1993; 8 (1): 23-33. (Pubitemid 23011155)
5. Chalon SA, Granier LA, Vandenhende FR, et al. Duloxetine increases serotonin and norepinephrine availability in healthy subjects: a double-blind, controlled study. Neuropsychopharmacology 2003; 28 (9): 1685-93. (Pubitemid 41070869)
6. Gahimer J, Wernicke J, Yalcin I, et al. A retrospective pooled analysis of duloxetine safety in 23,983 subjects. Curr Med Res Opin 2007; 23 (1): 175-84. (Pubitemid 46191681)
7. Berk M, du Plessis AD, Birkett M, et al. An open-label study of duloxetine hydrochloride, a mixed serotonin and noradrenaline reuptake inhibitor, in patients with DSM-III-R major depressive disorder. Lilly Duloxetine Depression Study Group. Int Clin Psychopharmacol 1997; 12 (3): 137-40. (Pubitemid 27283321)
8. Detke MJ, Lu Y, Goldstein DJ, et al. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry 2002; 63 (4): 308-15. (Pubitemid 34456358)
9. Detke MJ, Lu Y, Goldstein DJ, et al. Duloxetine 60mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatr Res 2002; 36 (6): 383-90. (Pubitemid 35254112)
10. Detke MJ, Wiltse CG, Mallinckrodt CH, et al. Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetinecontrolled trial. Eur Neuropsychopharmacol 2004; 14 (6): 457-70. (Pubitemid 39626894)
11. Goldstein DJ, LuY,DetkeMJ, et al. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol 2004; 24 (4): 389-99. (Pubitemid 38944137)
12. Nelson JC, Wohlreich MM, Mallinckrodt CH, et al. Duloxetine for the treatment of major depressive disorder in older patients. Am J Geriatr Psychiatry 2005; 13 (3): 227-35. (Pubitemid 41031091)
13. Nemeroff CB, Schatzberg AF, Goldstein DJ, et al. Duloxetine for the treatment of major depressive disorder. Psychopharmacol Bull 2002; 36 (4): 106-32.
14. Goldstein DJ, Lu Y, Detke MJ, et al. Duloxetine vs placebo in patients with painful diabetic neuropathy. Pain 2005; 116 (1-2): 109-18. (Pubitemid 40828506)
15. Raskin J, Pritchett YL, Wang F, et al. A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Pain Med 2005; 6 (5): 346-56. (Pubitemid 41727332)
16. Allgulander C, Hartford J, Russell J, et al. Pharmacotherapy of generalized anxiety disorder: results of duloxetine treatment from a pooled analysis of three clinical trials. Curr Med Res Opin 2007 Jun; 23 (6): 1245-52. (Pubitemid 46998433)
17. Hartford J, Kornstein S, Liebowitz M, et al. Duloxetine as an SNRI treatment for generalized anxiety disorder: results from a placebo and active-controlled trial. Int Clin Psychopharmacol 2007; 22 (3): 167-74. (Pubitemid 46559873)
18. Russell JM,Weisberg R, Fava M, et al. Efficacy of duloxetine in the treatment of generalized anxiety disorder in patients with clinically significant pain symptoms. Depress Anxiety 2008; 25 (7): E1-11.
19. Rynn M, Russell J, Erickson J, et al. Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial. Depress Anxiety 2008; 25 (3): 182-9. (Pubitemid 351499896)
20. Arnold LM, Lu Y, Crofford LJ, et al. 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 (9): 2974-84. (Pubitemid 39209537)
21. Guay DR. Duloxetine for management of stress urinary incontinence. Am J Geriatr Pharmacother 2005; 3 (1): 25-38. (Pubitemid 41122356)
22. Millard RJ, MooreK,Rencken R, et al. Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial. BJU Int 2004; 93 (3): 311-8. (Pubitemid 38253575)
23. Wernicke JF, Gahimer J, Yalcin I, et al. Safety and adverse event profile of duloxetine. Expert Opin Drug Saf 2005; 4 (6): 987-93. (Pubitemid 41671597)
24. Lobo ED, Bergstrom RF, Reddy S, et al. In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. Clin Pharmacokinet 2008; 47 (3): 191-202.
25. Lobo ED, Quinlan T, O'Brien L, et al. Population pharmacokinetics of orally administered duloxetine in patients: implications for dosing recommendation. Clin Pharmacokinet 2009; 48 (3): 189-97.
26. Chan C, Yeo KP, Pan AX, et al. Duloxetine pharmacokinetics are similar in Japanese and Caucasian subjects. Br J Clin Pharmacol 2007; 63 (3): 310-4.
27. Kuan HY, Reddy S, Zhang L, et al. Duloxetine single- and multiple-dose pharmacokinetics in healthy subjects [abstract]. Annual Meeting, American Association of Pharmaceutical Scientists; 2002 Nov 10-14; Toronto (ON).
28. Lobo ED, Loghin C, Knadler MP, et al. Pharmacokinetics of duloxetine in breast milk and plasma of healthy postpartum women. Clin Pharmacokinet 2008; 47 (2): 103-9.
29. Skinner MH, Kuan HY, Pan A, et al. Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. Clin Pharmacol Ther 2003; 73 (3): 170-7. (Pubitemid 36269668)
30. Skinner MH, Skerjanec A, Seger ME, et al. The effect of food and bedtime administration on duloxetine pharmacokinetics [abstract]. Clin Pharmacol Ther 2000; 67 (2): 129.
31. Sharma A, Goldberg MJ, Cerimele BJ. Pharmacokinetics and safety of duloxetine, a dual-serotonin and norepinephrine reuptake inhibitor. J Clin Pharmacol 2000; 40 (2): 161-7.
32. Cymbalta- (duloxetine hydrochloride) capsules [package insert]. Indianapolis (IN): Eli Lilly Pharmaceuticals, 2008.
33. Benet LZ, Hoener BA. Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther 2002; 71 (3): 115-21. (Pubitemid 34271114)
34. Rolan PE. Plasma protein binding displacement interactions: why are they still regarded as clinically important? Br J Clin Pharmacol 1994; 37 (2): 125-8. (Pubitemid 24213753)
35. Takano A, Suzuki K, Kosaka J, et al. A dose-finding study of duloxetine based on serotonin transporter occupancy. Psychopharmacology (Berl) 2006; 185 (3): 395-9.
36. Lantz RJ, Gillespie TA, Rash TJ, et al. Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects. Drug Metab Dispos 2003; 31 (9): 1142-50. (Pubitemid 37048286)
37. Kuo F, Gillespie TA, Kulanthaivel P, et al. Synthesis and biological activity of some known and putative duloxetine metabolites. Bioorg Med Chem Lett 2004; 14 (13): 3481-6. (Pubitemid 38737151)
38. Ring B, Gillespe JS, Kasper SC, et al. Interaction of duloxetine with human cytochrome P450 [abstract]. Drug Metab Rev 2003; 35 (S2): 181.
39. Relling MV, Lin JS, Ayers GD, et al. Racial and gender differences in Nacetyltransferase, xanthine oxidase, and CYP1A2 activities. Clin Pharmacol Ther 1992; 52 (6): 643-58. (Pubitemid 23001871)
40. Schrenk D, Brockmeier D, Morike K, et al. A distribution study of CYP1A2 phenotypes among smokers and non-smokers in a cohort of healthy Caucasian volunteers. Eur J Clin Pharmacol 1998; 53 (5): 361-7. (Pubitemid 28067979)
41. Fric M, Pfuhlmann B, Laux G, et al. The influence of smoking on the serum level of duloxetine. Pharmacopsychiatry 2008; 41 (4): 151-5.
42. Skinner MH, Kuan HY, Skerjanec A, et al. Effect of age on the pharmacokinetics of duloxetine in women. Br J Clin Pharmacol 2004; 57 (1): 54-61. (Pubitemid 38067950)
43. Tianmei S, Knadler MP, Lim MT, et al. Pharmacokinetics and tolerability of duloxetine following oral administration to healthy Chinese subjects. Clin Pharmacokinet 2007; 46 (9): 767-75. (Pubitemid 47347448)
44. Ma N, Zhang BK, Li HD, et al. Determination of duloxetine in human plasma via LC/MS and subsequent application to a pharmacokinetic study in healthy Chinese volunteers. Clin Chim Acta 2007; 380 (1-2): 100-5. (Pubitemid 46498036)
45. Suri A, Reddy S, Gonzales C, et al. Duloxetine pharmacokinetics in cirrhotics compared with healthy subjects. Int J Clin Pharmacol Ther 2005; 43 (2): 78-84. (Pubitemid 40298058)
46. Lobo ED, Heathman M, Kuan HY, et al. Analysis of a single-dose phase I study and pooled steady-state data from phase II/III trials. Clin Pharmacokinet 2010; 49 (5): 311-21.
47. Bjornsson TD, Callaghan JT, Einolf HJ, et al. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharmacol 2003; 43 (5): 443-69. (Pubitemid 36506147)
48. Sathirakul K, Teng L, Yeo KP, et al. Impact of gastric pH and the presence of activated charcoal on the absorption of duloxetine [abstract]. Clin Pharmacol Ther 2002; 71 (2): 18.
49. Small D, Loghin C, Lucas R, et al. Pharmacokinetic evaluation of combined duloxetine and fluvoxamine dosing in CYP2D6 poor metabolizers [abstract]. Clin Pharmacol Ther 2005; 77 (2): 37.
50. Patroneva A, Connolly SM, Fatato P, et al. An assessment of drug-drug interactions: the effect of desvenlafaxine and duloxetine on the pharmacokinetics of the CYP2D6 probe desipramine in healthy subjects. Drug Metab Dispos 2008; 36 (12): 2484-91.
51. Hua TC, Pan A, Chan C, et al. Effect of duloxetine on tolterodine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2004; 57 (5): 652-6. (Pubitemid 38582186)
52. Preskorn SH, Greenblatt DJ, Flockhart D, et al. Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. J Clin Psychopharmacol 2007; 27 (1): 28-34. (Pubitemid 46105760)
53. de LJ, Armstrong SC, Cozza KL. The dosing of atypical antipsychotics. Psychosomatics 2005; 46 (3): 262-73. (Pubitemid 40594318)
54. Englisch S, Knopf U, Scharnholz B, et al. Duloxetine for major depressive episodes in the course of psychotic disorders: an observational clinical trial. J Psychopharmacol 2009; 23 (8): 875-82.
55. Sheffrin M, Driscoll HC, Lenze EJ, et al. Pilot study of augmentation with aripiprazole for incomplete response in late-life depression: getting to remission. J Clin Psychiatry 2009; 70 (2): 208-13.
56. Derby MA, Zhang L, Chappell JC, et al. The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate. J Cardiovasc Pharmacol 2007; 49 (6): 384-93. (Pubitemid 47000313)
57. Wernicke J, LledoA, Raskin J, et al. An evaluation of the cardiovascular safety profile of duloxetine: findings from 42 placebo-controlled studies. Drug Saf 2007; 30 (5): 437-55. (Pubitemid 46740340)
58. Zhang L, Chappell J, Gonzales CR, et al. QT effects of duloxetine at supratherapeutic doses: a placebo and positive controlled study. J Cardiovasc Pharmacol 2007; 49 (3): 146-53. (Pubitemid 46579948)
59. Chalon SA, Vandenhende F, Ertle S. Combined administration of duloxetine (DU) and lorazepam (LO): a pharmacokinetic (PK) and pharmacodynamic (PD) study [abstract]. Clin Pharmacol Ther 2005; 77: 65.
60. Skinner MH, Weerakkody G. Duloxetine does not exacerbate the effects of alcohol on psychometric tests [abstract]. Clin Pharmacol Ther 2002; 71 (2): P53.
61. Monastero R, Camarda R, Camarda C. Potential drug-drug interaction between duloxetine and acenocoumarol in a patient with Alzheimer's disease. Clin Ther 2007; 29 (12): 2706-9.
62. Glueck CJ, Khalil Q, Winiarska M, et al. Interaction of duloxetine and warfarin causing severe elevation of international normalized ratio. JAMA 2006; 295 (13): 1517-8.
63. de Abajo FJ, Rodriguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ 1999; 319 (7217): 1106-9. (Pubitemid 29494721)
64. Chappell J, He J, Knadler MP, et al. Effects of duloxetine on the pharmacodynamics and pharmacokinetics of warfarin at steady-state in healthy subjects. J Clin Pharmacol 2009; 49 (12): 1456-66.
65. Baldessarini RJ. Drugs and the treatment of psychiatric disorders: depression and anxiety. In: Hardman JG, Limbird LE, Gilman AG, editors. Goodman and Gilman's: the pharmacological basis of therapeutics. New York: McGraw-Hill, 2001: 447-83.
66. Strouse TB, Kerrihard TN, Forscher CA, et al. Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine. J Clin Psychopharmacol 2006; 26 (6): 681-3. (Pubitemid 44772758)
67. Jimenez-Genchi A. Immediate switching from moclobemide to duloxetine may induce serotonin syndrome. J Clin Psychiatry 2006; 67 (11): 1821-2. (Pubitemid 44955170)
68. Waldschmitt C, Vogel F, Pfuhlmann B, et al. Duloxetine serum concentrations and clinical effects: data from a therapeutic drug monitoring (TDM) survey. Pharmacopsychiatry 2009; 42 (5): 189-93