SCHOOL OF MEDICINE

Department of Medicine

Clinical Pharmacology

2D6 REFERENCES

 2D6 SUBSTRATES: 

ALPRENOLOL
Polymorphic drug oxidation in humans. [ PMID 6714436 ]
Eichelbaum M.
Fed Proc 1984 May 15;43(8):2298-2302.

Competitive inhibition of sparteine oxidation in human liver by beta-adrenoceptor antagonists and other cardiovascular drugs. [ PMID 6141510 ]
Otton SV, Inaba T, Kalow W.
Life Sci 1984 Jan 2;34(1):73-80.

AMITRIPTYLINE
Amitriptyline metabolism: association with debrisoquin hydroxylation in nonsmokers. [ PMID 3956053 ]
Mellstrom B, Sawe J, Bertilsson L, Sjoqvist F.
Clin Pharmacol Ther. 1986 Apr; 39(4): 369-371.

Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin. [ PMID 3571939 ]
Baumann P, Jonzier-Perey M, Koeb L, Kupfer A, Tinguely D, Schopf J.
Int Clin Psychopharmacol. 1986 Apr; 1(2): 102-112.

AMPHETAMINE
The metabolic fate of amphetamine in man and other species. [ PMID 4985156 ]
Dring LG, Smith RL, Williams TR.
Biochem J 1970;425-435.

Introduction: human genetic variations in oxidative drug metabolism.
Smith RL.
Xenobiotica 1986;16:361-365.

ARIPIPRAZOLE
Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder. [ PMID 15257633 ]
Swainston Harrison T, Perry CM.
Drugs. 2004;64(15):1715-36.

ATOMOXETINE
Identification of the human cytochromes P450 responsible for atomoxetine metabolism. [ PMID 11854152 ]
Ring BJ, Gillespie JS, Eckstein JA, Wrighton SA.
Drug Metab Dispos. 2002 Mar;30(3):319-23.

BUFURALOL
Genetic polymorphism in drug oxidation: in vitro studies of human debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase activities. [ PMID 3966916 ]
Boobis AR, Murray S, Hampden CE, Davies DS.
Biochem Pharmacol 1985 Jan 1;34(1):65-71.

Characterization of a common genetic defect of cytochrome P-450 function (debrisoquine-sparteine type polymorphism)--increased Michaelis is Constant (Km) and loss of stereoselectivity of bufuralol 1'-hydroxylation in poor metabolizers. [ PMID 6508804 ]
Dayer P, Gasser R, Gut J, Kronbach T, Robertz GM, Eichelbaum M, Meyer UA.
Biochem Biophys Res Commun 1984 Nov 30;125(1):374-380.

Debrisoquine-type polymorphism of drug oxidation: purification from human liver of a cytochrome P450 isozyme with high activity for bufuralol hydroxylation. [ PMID 6146537 ]
Gut J, Gasser R, Dayer P, Kronbach T, Catin T, Meyer UA.
FEBS Lett 1984 Aug 6;173(2):287-290.

Enzymatic basis of the debrisoquine/sparteine-type genetic polymorphism of drug oxidation. Characterization of bufuralol 1'-hydroxylation in liver microsomes of in vivo phenotyped carriers of the genetic deficiency. [ PMID 3689440 ]
Dayer P, Kronbach T, Eichelbaum M, Meyer UA.
Biochem Pharmacol 1987 Dec 1;36(23):4145-4152.

CARVEDILOL

CHLORPHENIRAMINE

CHLORPROMAZINE

CLOMIPRAMINE
Pharmacogenetics of antidepressants: clinical aspects. [ PMID 9265947 ]
Bertilsson L, Dahl ML, Tybring G.
Acta Psychiatr Scand Suppl 1997;391:14-21.

CLONIDINE
CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance. [ PMID 20570945 ]
Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF.
Drug Metab Dispos. 2010 Sep;38(9):1393-6.

CODEINE
Impact of environmental and genetic factors on codeine analgesia. [ PMID 1782973 ]
Desmeules J, Gascon MP, Dayer P, Magistris M.
Eur J Clin Pharmacol 1991;41(1):23-26.

DEBRISOQUINE
Polymorphism of carbon oxidation of drugs and clinical implications. [ PMID 151576 ]
Sloan TP, Mahgoub A, Lancaster R, Idle JR, Smith RL.
Br Med J. 1978 Sep 2; 2(6138): 655-657.

Genetically determined defects of oxidation at carbon centers of drugs. [ PMID 76883 ]
Smith RL, Idle JR, Mahgoub AA, Sloan TP, Lancaster R.
Lancet. 1978 Apr 29; 1(8070): 943-944.

Hypotensive response to debrisoquine and hydroxylation phenotype. [ PMID 642709 ]
Idle JR, Mahgoub A, Lancaster R, Smith RL.
Life Sci. 1978 Mar; 22(11): 979-983.

Polymorphic hydroxylation of Debrisoquine in man. [ PMID 71400 ]
Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL.
Lancet. 1977 Sep 17; 2(8038): 584-586.

DESIPRAMINE
Polymorphic 2-hydroxylation of desipramine: A population and family study. [ PMID 8359181 ]
Dahl ML, Iselius L, Alm C, Svensson JO, Lee D, Johansson I. Ingelman-Sundberg M. Sjoqvist F.
Eur J Clin Pharmacol 1993;44:445-450.

DEXFENFLURAMINE
The influence of the sparteine/debrisoquine genetic polymorphism on the disposition of dexfenfluramine. [ PMID 8730977 ]
Gross AS, Phillips AC, Rieutord A, Shenfield GM.
Br J Clin Pharmacol 1996;41:311-317.

DEXTROMETHORPHAN
Debrisoquine and dextromethorphan phenotyping and antidepressant treatment. [ PMID 2020918 ]
Perault MC, Bouquet S, Bertschy G, Vandel S, Chakroun R, Guibert S, Vandel B.
Therapie 1991 Jan;46(1):1-3.

Doxepin inhibits CYP2D6 activity in vivo. [ PMID 15520506 ]
Szewczuk-Boguslawska M, Kiejna A, Beszlej JA, Orzechowska-Juzwenko K, Milejski P.
Pol J Pharmacol. 2004 Jul-Aug;56(4):491-4.

DONEPEZIL
Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics. [ PMID 19300564 ]
Cacabelos R.
Neuropsychiatr Dis Treat. 2007 Jun;3(3):303-33.

Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer's disease patients. [ PMID 16845507 ]
Varsaldi F, Miglio G, Scordo MG, Dahl ML, Villa LM, Biolcati A, Lombardi G.
Eur J Clin Pharmacol. 2006 Sep;62(9):721-6.

DULOXETINE
Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. [ PMID 12621382 ]
Skinner MH, Kuan HY, Pan A, Sathirakul K, Knadler MP, Gonzales CR, Yeo KP, Reddy S, Lim M, Ayan-Oshodi M, Wise SD.
Clin Pharmacol Ther. 2003 Mar;73(3):170-7.

ENCAINIDE
Effect of low dose quinidine on encainide pharmacokinetics and pharmacodynamics. Influence of genetic polymorphism. [ PMID 2496225 ]
Funck-Brentano C, Turgeon J, Woosley RL, Roden DM.
J Pharmacol Exp Ther 1989 Apr;249(1):134-42.

FLECAINIDE
Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone. [ PMID 8143391 ]
Funck-Brentano C, Becquemont L, Kroemer HK, Buhl K, Knebel NG, Eichelbaum M, Jaillon P.
Clin Pharmacol Ther 1994 Mar;55(3):256-269.

FLUOXETINE
The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin. [ PMID 8941024 ]
Hamelin BA, Turgeon J, Vallee F, Belanger P-M, Paquet F, LeBel M.
Clin Pharmacol Ther 1996;60:512-521.

FLUVOXAMINE
Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYP1A2 activity. [ PMID 8823236 ]
Carillo JA, Dahl M-L, Svennson J-O, Alm C, Rodriguez I, Bertillson L.
Clin Pharmacol Ther 1996;60:183-190.

HISTAMINE H1 receptor antagonists
In Vitro Characterization of Cytochrome P450 2D6 Inhibition by Classic Histamine H1 Receptor Antagonists. [ PMID 9616188 ]
Drug Metab Dispos. 1998 Jun;26(6):536-9.

HALOPERIDOL
Haloperidol disposition is dependent on the debrisoquine hydroxylation phenotype: increased plasma levels of the reduced metabolite in poor metabolizers. [ PMID 1412613 ]
Llerena, A., Dahl, M.-L., Ekqvist, B., and Bertilsson, L.
Ther Drug Monit 14:261-264, 1992.

IMIPRAMINE
Role of P450 IID6, the target of the sparteine-debrisoquin oxidation polymorphism, in the metabolism of imipramine. [ PMID 2060250 ]
Brøsen K, Zeugin T, Meyer UA.
Clin Pharmacol Ther 1991;49(6):609-617.

LIDOCAINE
The pharmacokinetic and pharmacodynamic interaction between propafenone and lidocaine. [ PMID 8422740 ]
Ujhelyi MR, O'Rangers EA, Fan C, Kluger J, Pharand C, Chow MS.
Clin Pharmacol Ther. 1993 Jan;53(1):38-48.

METOCLOPRAMIDE

METHOXYAMPHETAMINE

S-METOPROLOL
Influence of amino acid residue 374 of cytochrome P-450 2D6 (CYP2D6) on the regio- and enantio-selective metabolism of metoprolol. [ PMID 8687412 ]
Ellis SW, Rowland K, Ackland MJ, Rekka E, Simula AP, Lennard MS, Wolf CR, Tucker GT.
Biochem J. 1996 Jun 1; 316( Pt 2): 647-654.

Influence of debrisoquine oxidation phenotype on exercise tolerance and subjective fatigue after metoprolol and atenolol in healthy subjects. [ PMID 2049246 ]
Lewis RV, Ramsay LE, Jackson PR, Yeo WW, Lennard MS, Tucker GT.
Br J Clin Pharmacol 1991 Apr;31(4):391-398.

Debrisoquine phenotype and the pharmacokinetics and beta-2 receptor pharmacodynamics of metoprolol and its enantiomers. [ PMID 1848636 ]
Jonkers RE, Koopmans RP, Portier EJ, van Boxtel CJ.
J Pharmacol Exp Ther 1991 Mar;256(3):959-966.

Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol. [ PMID 2874665 ]
Lennard MS, Tucker GT, Silas JH, Woods HF.
Xenobiotica 1986 May;16(5):435-447.

Single-dose quinidine treatment inhibits metoprolol oxidation in extensive metabolizers. [ PMID 3709620 ]
Leemann T, Dayer P, Meyer UA.
Eur J Clin Pharmacol 1986;29(6):739-741.

Metoprolol metabolism and debrisoquine oxidation polymorphism--population and family studies. [ PMID 2868742 ]
McGourty JC, Silas JH, Lennard MS, Tucker GT, Woods HF.
Br J Clin Pharmacol 1985 Dec;20(6):555-566.

Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers. [ PMID 6641087 ]
Lennard MS, Tucker GT, Silas JH, Freestone S, Ramsay LE, Woods HF.
Clin Pharmacol Ther 1983 Dec;34(6):732-737.

Oxidation phenotype--a major determinant of metoprolol metabolism and response. [ PMID 7144837 ]
Lennard MS, Silas JH, Freestone S, Ramsay LE, Tucker GT, Woods HF.
N Engl J Med 1982 Dec 16;307(25):1558-1560.

Defective metabolism of metoprolol in poor hydroxylators of debrisoquine. [ PMID 6125207 ]
Lennard MS, Silas JH, Freestone S, Trevethick J.
Br J Clin Pharmacol 1982 Aug;14(2):301-303.

MEXILETINE

MINAPRINE
Involvement of the cytochrome P-450IID subfamily in minaprine 4-hydroxylation by human hepatic microsomes. [ PMID 1352227 ]
Marre F, Fabre G, Lacarelle B, Bourrie M, Catalin J, Berger Y, Rahmani R, Cano J.
Drug Metab Dispos 20(2):316-321, 1992.

NEBIVOLOL
Pharmacokinetic disposition of nebivolol in extensive and poor CYP2D6 metabolizers.
Andrew A. Shaw, John Ziemniak, Shiyao Liu, Scott W. Chervenick, Russell J. Rackley.
American Society for Clinical Pharacology and Therapeutics. March 2-6, 2005. Orlando, FL.

NORTRIPTYLINE

ONDANSETRON

OXYCODONE

PAROXETINE

PERHEXILINE

PERPHENAZINE
Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in human beings. [ PMID 2743709 ]
Dahl-Puustinen, M.-L., Liden, A., Alm, C., Nordin, C., and Bertilsson, L.
Clin Pharmacol Ther 46(1):78-81, 1989.

Steady state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism. [ PMID 8689810 ]
Linnet K, Wiborg O.
Clin Pharmacol Ther 1996;60:41-47.

Inhibitors of imipramine metabolism by human liver microsomes. [ PMID 1389950 ]
Skjelbo, E. and Brosen, K.
Br J Clin Pharmacol 34:256-261, 1992.

PHENACETIN

PHENFORMIN

PROMETHAZINE
Akathisia with combined use of midodrine and promethazine. [ PMID 16670408 ]
Platts SH, Shi SJ, Meck JV.
JAMA. 2006 May 3;295(17):2000-1.

PROPAFENONE
The role of genetically-determined polymorphic drug metabolism in the beta-blockade produced by propafenone. [ PMID 1971708 ]
Lee JT, Kroemer HK, Silberstein DJ, Funck-Brentano C, Lineberry MD, Wood AJJ, Roden DM, Woosley RL.
N Eng J Med 1990;332(25):1764-1768.

PROPANOLOL

QUANOXAN

RISPERIDONE
Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. [ PMID 7690693 ]
Huang ML, Van Peer A, Woestenborghs R, De Coster R, Heykants J, Jansen AA, Zylicz Z, Visscher HW, Jonkman JH.
Clin Pharmacol Ther. 1993 Sep; 54(3): 257-268.

SPARTEINE
Pharmacogenetic covariation of defective N-oxidation of sparteine and 4-hydroxylation of debrisoquine. [ PMID 7371707 ]
Bertilsson L, Dengler HJ, Eichelbaum M, Schulz HU.
Eur J Clin Pharmacol. 1980 Feb; 17(2): 153-155.

Influence of the defective metabolism of sparteine on its pharmacokinetics. [ PMID 499319 ]
Eichelbaum M, Spannbrucker N, Dengler HJ.
Eur J Clin Pharmacol. 1979 Sep; 16(3): 189-194.

Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. [ PMID 499318 ]
Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ,
Eur J Clin Pharmacol. 1979 Sep; 16(3): 183-187.

A human genetic defect in the metabolism of sparteine. [ PMID 741903 ]
Spannbrucker N, Eichelbaum M, Steinke B, Dengler HJ.
Verh Dtsch Ges Inn Med. 1978; 84: 1125-1127 German.

TAMOXIFEN
Delineation of human cytochromes P450 involved in the metabolism of tamoxifen.
Daniels L, Blankson EA, Henderson CJ, Harris AH, Wolf CR, Lennard MS, Tucker GT.
Br J Clin Pharmacol 33:153P, 1992.

Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. [ PMID 14652237 ]
Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA.
J Natl Cancer Inst. 2003 Dec 3;95(23):1734-5.

THIORIDAZINE
Plasma levels of thioridazine and metabolites are influenced by the debrisoquin hydroxylation phenotype. [ PMID 2007317 ]
von Bahr C, Movin G, Nordon C, Liden A, Hammarlund-Udenaes,M, Hedberg,A, Ring H, Sjoqvist F.
Clin Pharmacol Ther 49:234-240, 1991.

TIMOLOL
Pharmacogenetic explanation for excessive beta-blockade following timolol eye drops. Potential for oral-ophthalmic drug interaction. [ PMID 7474246 ]
Edeki TI, He H, Wood AJ.
JAMA. 1995 Nov 22; 274(20): 1611-1613.

Systemic absorption of ocular timolol in poor and extensive metabolizers of debrisoquine. [ PMID 1919275 ]
Huupponen R, Kaila T, Lahdes K, Salminen L, Iisalo E.
J Ocul Pharmacol. 1991; 7(2): 183-187.

The effects of timolol on intraocular pressure and exercise heart rate in poor and extensive debrisoquine metabolizers. [ PMID 2099359 ]
al-Sereiti MR, Edeki T, Lledo P, Turner P.
Int J Clin Pharmacol Res 1990;10(6):339-345.

Prevalence of debrisoquine oxidation phenotypes in glaucoma patients. [ PMID 2787298 ]
Salminen L, Lindberg R, Toivari HR, Huupponen R, Kaila T, Iisalo E.
Int Ophthalmol 1989 Jan;13(1-2):91-93.

Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol. [ PMID 2874665 ]
Lennard MS, Tucker GT, Silas JH, Woods HF.
Xenobiotica. 1986 May; 16(5): 435-447.

Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin. [ PMID 2864157 ]
McGourty JC, Silas JH, Fleming JJ, McBurney A, Ward JW.
Clin Pharmacol Ther. 1985 Oct; 38(4): 409-413.

Timolol and atenolol: relationships between oxidation phenotype, pharmacokinetics and pharmacodynamics. [ PMID 2859048 ]
Lewis RV, Lennard MS, Jackson PR, Tucker GT, Ramsay LE, Woods HF.
Br J Clin Pharmacol. 1985 Mar; 19(3): 329-333.

Timolol determination in plasma and urine by high-performance liquid chromatography with ultraviolet detection. [ PMID 4019651 ]
Lennard MS, Parkin S.
J Chromatogr. 1985 Feb 27; 338(1): 249-252.

Polymorphic metabolism of the beta-adrenoreceptor blocking drugs and its clinical relevance [ PMID 2865154 ]
Smith RL.
Eur J Clin Pharmacol. 1985; 28 Suppl: 77-84.

TRAMADOL
Pharmacology of tramadol. [ PMID 9190321 ]
Dayer P, Desmeules J, Collart L.
Drugs 1997;53 Suppl 2:18-24.

A rapid and simple CYP2D6 genotyping assay--case study with the analgetic tramadol. [ PMID 14624403 ]
Borlak J, Hermann R, Erb K, Thum T.
Metabolism. 2003 Nov;52(11):1439-43.

VENLAFAXINE
O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. [ PMID 10192828 ]
Fogelman SM, Schmider J, Venkatakrishnan K, von Moltke LL, Harmatz JS, Shader RI, Greenblatt DJ.
Neuropsychopharmacology 1999 May;20(5):480-90.

ZUCLOPENTHIXOL
Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? [ PMID 12083975 ]
Dahl ML.
Clin Pharmacokinet. 2002;41(7):453-70.

Pharmacogenetics of classical and new antipsychotic drugs. [ PMID 10688273 ]
Otani K, Aoshima T.
Ther Drug Monit. 2000 Feb;22(1):118-21.

 


 2D6 INHIBITORS: 

AMIODARONE
Effect of amiodarone on the serum concentration/dose ratio of metoprolol in patients with cardiac arrhythmia. [ PMID 17220566 ]
Fukumoto K, Kobayashi T, Tachibana K, Kato R, Tanaka K, Komamura K, Kamakura S, Kitakaze M, Ueno K.
Drug Metab Pharmacokinet. 2006 Dec;21(6):501-5.

Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. [ PMID 10718780 ]
Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T.
Br J Clin Pharmacol. 2000 Mar;49(3):244-53.

The inhibitory effect of amiodarone and desethylamiodarone on dextromethorphan O-demethylation in human and rat liver microsomes. [ PMID 7897605 ]
Jaruratanasirikul S, Hortiwakul R.
J Pharm Pharmacol. 1994 Nov;46(11):933-5.

BUPROPION
Inhibition of CYP2D6 activity by bupropion. [ PMID 15876900 ]
Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, Adson DE.
J Clin Psychopharmacol. 2005 Jun;25(3):226-9.

CELECOXIB
Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans. [ PMID 12891223 ]
Werner U, Werner D, Rau T, Fromm MF, Hinz B, Brune K.
Clin Pharmacol Ther. 2003 Aug;74(2):130-7.

CIMETIDINE
The effect of cimetidine on dextromethorphan O-demethylase activity of human liver microsomes and recombinant CYP2D6. [ PMID 16680870 ]
Madeira M, Levine M, Chang TK, Mirfazaelian A, Bellward GD.
Drug Metab Dispos. 2004 Apr;32(4):460-7.

Differential inhibition of individual human liver cytochromes P450 by cimetidine. [ PMID 1955133 ]
Knodell RG, Browne DG, Gwozdz GP, Brian WR, Guengerich FP.
Gastroenterology 1991;101:1680-1691.

CINACALCET
Effect of cinacalcet hydrochloride, a new calcimimetic agent, on the pharmacokinetics of dextromethorphan: in vitro and clinical studies. [ PMID 17652181 ]
Nakashima D, Takama H, Ogasawara Y, Kawakami T, Nishitoba T, Hoshi S, Uchida E, Tanaka H.
J Clin Pharmacol. 2007 Oct;47(10):1311-9.

Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. [ PMID 16680561 ]
Harris RZ, Salfi M, Posvar E, Hoelscher D, Padhi D.
Eur J Clin Pharmacol. 2007 Feb;63(2):159-63.

CITALOPRAM
Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. [ PMID 9068931 ]
Preskorn SH.
Clin Pharmacokinet. 1997;32 Suppl 1:1-21.

CLOMIPRAMINE
Cytochrome p450 IID6, its role in psychopharmacology. [ PMID 7741408 ]
Lamard L, Perault MC, Bouquet S, Guibert S.
Ann Med Psychol (Paris) 1995 Feb;153(2):140-143.

COCAINE
Neuronal cytochrome P450IID1 (debrisoquine/sparteine-type): Potent inhibition of activity by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. [ PMID 1857341 ]
Tyndale RF, Sunahara RK, Inaba T, Kalow W, Gonzalez FJ, Niznik HB.
Mol Pharmacol 40:63-68, 1991.

DOXORUBICINE
Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. [ PMID 8258200 ]
Le Guellec C, Lacarelle B, Catalin J, Durand A.
Cancer Chemother Pharmacol 32:491-495, 1993.

DULOXETINE
Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. [ PMID 12621382 ]
Skinner MH, Kuan HY, Pan A, Sathirakul K, Knadler MP, Gonzales CR, Yeo KP, Reddy S, Lim M, Ayan-Oshodi M, Wise SD.
Clin Pharmacol Ther. 2003 Mar;73(3):170-7.

ESCITALOPRAM
Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. [ PMID 17224709 ]
Preskorn SH, Greenblatt DJ, Flockhart D, Luo Y, Perloff ES, Harmatz JS, Baker B, Klick-Davis A, Desta Z, Burt T.
J Clin Psychopharmacol. 2007 Feb;27(1):28-34.

FLUOXETINE
Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance. [ PMID 10583026 ]
Brynne N, Svanström C, Aberg-Wistedt A, Hallén B, Bertilsson L.
Br J Clin Pharmacol. 1999 Oct;48(4):553-63.

Inhibitory effects of psychotropic drugs on mexiletine metabolism in human liver microsomes: prediction of in vivo drug interactions. [ PMID 16192107 ]
Hara Y, Nakajima M, Miyamoto KI, Yokoi T.
Xenobiotica. 2005 Jun;35(6):549-60.

HALOFANTRINE
Halofantrine and chloroquine inhibit CYP2D6 activity in healthy Zambians. [ PMID 10896408 ]
Simooya OO, Sijumbil G, Lennard MS, Tucker GT.
Br J Clin Pharmacol. 1998 Mar;45(3):315-7.

An investigation of the interaction between halofantrine, CYP2D6 and CYP3A4: studies with human liver microsomes and heterologous enzyme expression systems. [ PMID 8554939 ]
Halliday RC, Jones BC, Smith DA, Kitteringham NR, Park BK.
Br J Clin Pharmacol. 1995 Oct;40(4):369-78.

HISTAMINE H1 RECEPTOR ANTAGONISTS
Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia. [ PMID 17089107 ]
Saruwatari J, Matsunaga M, Ikeda K, Nakao M, Oniki K, Seo T, Mihara S, Marubayashi T, Kamataki T, Nakagawa K.
Eur J Clin Pharmacol. 2006 Dec;62(12):995-1001.

LEVOMEPROMAZINE
O-demethylation of codeine to morphine inhibited by low-dose levomepromazine. [ PMID 19308365 ]
Vevelstad M, Pettersen S, Tallaksen C, Brørs O.
Eur J Clin Pharmacol. 2009 Mar 24.

MIDODRINE
Akathisia with combined use of midodrine and promethazine. [ PMID 16670408 ]
Platts SH, Shi SJ, Meck JV.
JAMA. 2006 May 3;295(17):2000-1.

METHADONE
Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone. [ PMID 8448065 ]
Wu D, Otton SV, Sproule BA, Busto U, Inaba T, Kalow W, Sellers EM.
Br J Clin Pharmacol 1993 Jan;35(1):30-34.

MOCLOBEMIDE
Moclobemide: a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6 and CYP1A2: A panel study. [ PMID 7781267 ]
Gram LF, Guentert TW, Grange S, Vistisen K, Brøsen K.
Clin Pharmacol Ther 1995;57(6):670-677.

PAROXETINE
Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: comparison with fluoxetine and quinidine. [ PMID 12584155 ]
Bertelsen KM, Venkatakrishnan K, Von Moltke LL, Obach RS, Greenblatt DJ.
Drug Metab Dispos. 2003 Mar;31(3):289-93.

CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. [ PMID 15632378 ]
Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA.
J Natl Cancer Inst. 2005 Jan 5;97(1):30-9.

Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. [ PMID 14652237 ]
Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA.
J Natl Cancer Inst. 2003 Dec 3;95(23):1758-64.

Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. [ PMID 8513845 ]
Brosen K, Hansen JG, Nielsen KK, Sindrup SH, Gram LF.
Eur J Clin Pharmacol 44:349-355, 1993.

Plasma concentrations of clozapine and its major metabolites during combined treatment with paroxetine or sertraline. [ PMID 11147928 ]
Spina E, Avenoso A, Salemi M, Facciolá G, Scordo MG, Ancione M, Madia A.
Pharmacopsychiatry. 2000 Nov;33(6):213-7.

CYP2D6 inhibition by selective serotonin reuptake inhibitors: analysis of achievable steady-state plasma concentrations and the effect of ultrarapid metabolism at CYP2D6. [ PMID 12173784 ]
Lam YW, Gaedigk A, Ereshefsky L, Alfaro CL, Simpson J.
Pharmacotherapy. 2002 Aug;22(8):1001-6.

QUINIDINE
Why is quinidine an inhibitor of cytochrome P450 2D6? The role of key active-site residues in quinidine binding. [ PMID 16162505 ]
McLaughlin LA, Paine MJ, Kemp CA, Maréchal JD, Flanagan JU, Ward CJ, Sutcliffe MJ, Roberts GC, Wolf CR.
J Biol Chem. 2005 Nov 18;280(46):38617-24.

Inhibition of desmethylimipramine 2-hydroxylation by drugs in human liver microsomes. [ PMID 4015690 ]
von Bahr C, Spina E, Birgersson C, Ericsson O, Göransson M, Henthorn T, Sjöqvist F.
Biochem Pharmacol. 1985 Jul 15;34(14):2501-5.

In vivo modulation of CYP enzymes by quinidine and rifampin. [ PMID 11061580 ]
Branch RA, Adedoyin A, Frye RF, Wilson JW, Romkes M.
Clin Pharmacol Ther. 2000 Oct;68(4):401-11.

Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. [ PMID 9758674 ]
von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI.
J Pharm Sci. 1998 Oct;87(10):1184-9.

REDUCED HALOPERIDOL
Oxidation of reduced haloperidol to haloperidol: involvement of human P450 2D6. [ PMID 1867960 ]
Tyndale RF, Kalow W, Inaba T.
Br J Clin Pharmacol 1991;31:655-660.

RITONAVIR
Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. [ PMID 8613951 ]
Kumar GN, Rodrigues AD, Buko AM, Denissen JF.
J Pharmacol Exp Ther 1996;277(1):423-431.

SERTRALINE
Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. [ PMID 17224709 ]
Preskorn SH, Greenblatt DJ, Flockhart D, Luo Y, Perloff ES, Harmatz JS, Baker B, Klick-Davis A, Desta Z, Burt T.
J Clin Psychopharmacol. 2007 Feb;27(1):28-34.

The effect of sertraline on the pharmacokinetics of desipramine and imipramine. [ PMID 9284850 ]
Kurtz DL, Bergstrom RF, Goldberg MJ, Cerimele BJ.
Clin Pharmacol Ther. 1997 Aug;62(2):145-56.

TERBINAFINE
Potent inhibition of cytochrome P-450 2D6-mediated dextromethorphan O-demethylation by terbinafine. [ PMID 10383919 ]
Abdel-Rahman SM, Marcucci K, Boge T, Gotschall RR, Kearns GL, Leeder JS.
Drug Metab Dispos. 1999 Jul;27(7):770-5.


 2D6 INDUCERS: 

DEXAMETHASONE

RIFAMPIN
The influence of enzyme induction on polymorphic sparteine oxidation.[ PMID 3741726 ]
Eichelbaum M, Mineshita S, Ohnhaus EE, Zekorn C.
Br J Clin Pharmacol 1986;22:49-53.

The genetic polymorphism of sparteine metabolism.[ PMID 3739368 ]
Eichelbaum M, Reetz K, Schmidt K, and Zekorn C.
Xenobiotica 16(5):465-481, 1986.