An in vitro mechanistic study to elucidate the desipramine/bupropion clinical drug-drug interaction

Drug Metabolism and Disposition

Volumn 36, Issue 7, 2008, Pages 1198-1201

  Reese, Melinda J ^a,b   Wurm, Robert M ^a,b   Muir, Keith T ^a,b   Generaux, Grant T ^a,b   St John Williams, Lisa ^a,b   Von J McConn, Dona ^a,b  

^a GLAXOSMITHKLINE   (United States)

^b THERAVANCE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMFEBUTAMONE; BUFURALOL; CYTOCHROME P450 2D6; DESIPRAMINE; DRUG METABOLITE; ERYTHROHYDROBUPROPION; RADAFAXINE; THREOHYDROBUPROPION;

AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CROSS REACTIVITY; DRUG METABOLISM; DRUG POTENCY; ENZYME INHIBITION; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; IC 50; IN VITRO STUDY; LIVER MICROSOME; MALE; MAXIMUM PLASMA CONCENTRATION; MULTIPLE DRUG DOSE; NORMAL HUMAN; OPEN STUDY; PRIORITY JOURNAL; SINGLE DRUG DOSE; VOLUNTEER;

ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; ANTIDEPRESSIVE AGENTS, TRICYCLIC; AREA UNDER CURVE; BUPROPION; CYTOCHROME P-450 CYP2D6; DESIPRAMINE; DRUG INTERACTIONS; ENZYME INHIBITORS; HUMANS; MICROSOMES, LIVER;

EID: 46449138007     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.107.020198     Document Type: Article

References (18)

1. Brøsen K, Hansen JG, Nielsen KK, Sindrup SH, and Gram LF (1993) Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. Eur J Clin Pharmacol 44:349-355.
2. Brøsen K, Klysner R, Gram LF, Otton SV, Bech P, and Bertilsson L (1986) Steady state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism. Eur J Clin Pharmacol 30:679-684.
3. Distlerath LM and Guengerich FP (1984) Characterization of human liver cytochrome P-450 involved in the oxidation of debrisoquine and other drugs by using antibodies raised to the analogous rat enzyme. Proc Natl Acad SciUSA 81:7348-7352.
4. Faucette SR, Hawke RL, Lecluyse EL, Shord SS, Yan B, Laethem RM, and Lindley CM (2000) Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. Drug Metab Dispos 28:1222-1230.
5. Findlay JWA, Van Wyck Fleet J, Smith PG, Butz RF, Hinton ML, Blum MR, and Schroeder DH (1981) Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects. Eur J Clin Pharmacol 21:127-135.
6. Golden RN, De Vane CL, Laizure SC, Rudorfer MV, Sherer MA, and Potter WZ (1988) Bupropion in depression. II. The role of metabolites in clinical outcome. Arch Gen Psychiatry 45:145-149.
7. Gram LF (1974) Metabolism of tricyclic antidepressants. Dan Med Bull 21:218-231.
8. Güzey C, Norstrom A, and Spigset O (2002) Change from the CYP2D6 extensive metabolizer to the poor metabolizer phenotype during treatment with bupropion. Ther Drug Monit 24:436-437.
9. Hesse LM, Nevkatakrishnan K, Court MH, von Moltke LL, Duan SX, Shader RI, and Greenblatt DJ (2000) 2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidipressants. Drug Metab Dispos 28:1176-1183.
10. Hinton LK, Galetin A, and Houston JB (2008) Multiple inhibition mechanisms and prediction of drug-drug interactions: status of metabolism and transporter models as exemplified by gemfibrozil-drug interactions. Pharm Res 25:1063-1074.
11. Ito K, Hallifax D, Obach RS, and Houston JB (2005) Impact of parallel pathways of drug elimination and multiple cytochrome P450 involvement on drug-drug interactions: CYP2D6 paradigm. Drug Metab Dispos 33:837-844.
12. Jefferson JW, Pradko JF, and Muir KT (2005) Bupropion for major depressive disorder: pharmacokinetics and formulation considerations. Clin Ther 27:1685-1695.
13. Kennedy SH, McCann SM, Masellis M, McIntyre RS, Raskin J, McKay G, and Baker GB (2002) Combining bupropion with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. J Clin Psychiatry 63:181-186.
14. Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, and Adson DE (2005) Inhibition of CYP2D6 activity by bupropion. J Clin Psychopharmacol 25:226-229.
15. Obach RS, Walsky RL, Venkatakrishnan K, Gaman EA, Houston JB, and Tremaine LM (2006) The utility of in vitro cytochrome P450 inhibition data in the prediction of drug-drug interactions. J Pharmacol Exp Ther 316:336-348.
16. Rostami-Hodjegan A and Tucker G (2004) "In silico" simulations to assess the "in vivo" consequences of "in vitro" metabolic drug-drug interactions. Drug Discov Today 1:441-448.
17. Schroeder DH (1983) Metabolism and kinetics of bupropion. J Clin Psychiatry 44:79-81.
18. Shad MU and Preskorn SH (1997) A possible bupropion and imipramine interaction. J Clin Psychopharmacol 17:118-119.