SCHOOL OF MEDICINE

Department of Medicine

Clinical Pharmacology

1A2 REFERENCES

 1A2 SUBSTRATES: 

AMITRIPTYLINE
Fluvoxamine-tricyclic antidepressant interaction. An accidental finding. [ PMID 1905641 ]
Bertschy G, Vandel S, Vandel B, Allers G, Volmat R.
Eur J Clin Pharmacol 1991;40(1):119-120. [Letter]

CAFFEINE
Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans. [ PMID 8738764 ]
Rasmussen BB, Brosen K.
Ther Drug Monit 1996 Jun;18(3):254-262.

Assays for CYP1A2 by testing in vivo metabolism of caffeine in humans. [ PMID 8791769 ]
Tang BK, Kalow W.
Methods Enzymol 1996;272:124-131.

CLOMIPRAMINE
Fluvoxamine-tricyclic antidepressant interaction. An accidental finding. [ PMID 1905641 ]
Bertschy G, Vandel S, Vandel B, Allers G, Volmat R.
Eur J Clin Pharmacol 1991;40(1):119-120. [Letter]

CLOZAPINE
Metabolism and bioactivation of clozapine by human liver in vitro. [ PMID 7891353 ]
Pirmohamed M, Williams D, Madden S, Templeton E, Park BK.
J Pharmacol Exp Ther 272(3):984-990, 1995.

Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. [ PMID 7893591 ]
Bertilsson L, Carrillo JA, Dahl ML, Llerena A, Alm C, Bondesson U, Lindström L, Rodriguez de la Rubia I, Ramos S, Benitez J.
Br J Clin Pharmacol 38:471-473, 1994.

CYCLOBENZAPRINE
Identification of Human Liver Cytochrome P450 Isoforms involved in the in vitro metabolism of cyclobenzaprine. [ PMID 8818577 ]
Wang RW, Liu L, Cheng H.
Drug Metab Dispos 1996;24(7):786-791.

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

ESTRADIOL
Differences in the cytochrome P-450 isoenzymes involved in the 2-hydroxylation of oestradiol and 17alpha-ethinyloestradiol. [ PMID 2327982 ]
Ball SE, Forrester LM, Wolf CR, Back DJ.
Biochem J 267:221-226, 1990.

HALOPERIDOL
Coadministration of fluvoxamine increases serum concentrations of haloperidol. [ PMID 7806690 ]
Daniel DG, Randolph C, Jaskiw G, Handel S, Williams T, Abi-Dargham A, Shoaf S, Egan M, Elkashef A, Liboff S, Linnoila M.
J Clin Psychopharmacol 14:340-343, 1994.

IMIPRAMINE
Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. [ PMID 9190854 ]
Koyama E, Chiba K, Tani M, Ishizaki T
J Pharmacol Exp Ther 1997 Jun;281(3):1199-1210

Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. [ PMID 8502233 ]
Lemoine A, Gautier JC, Azoulay D, Kiffel L, Belloc C, Guengerich FP, Maurel P, Beaune P, Leroux JP
Mol Pharmacol 1993 May;43(5):827-832

MEXILETINE
Role of specific cytochrome P450 enzymes in the N-oxidation of the antiarrhythmic agent mexiletine. [ PMID 12519691 ]
Labbé L, Abolfathi Z, Lessard E, Pakdel H, Beaune P, Turgeon J.
Xenobiotica. 2003 Jan;33(1):13-25.

Inhibition of human liver cytochrome P-450 1A2 by the class IB antiarrhythmics mexiletine, lidocaine, and tocainide. [ PMID 10215663 ]
Wei X, Dai R, Zhai S, Thummel KE, Friedman FK, Vestal RE.
J Pharmacol Exp Ther. 1999 May;289(2):853-8.

NAPROXEN
Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen. [ PMID 8866821 ]
Miners JO, Coulter S, Tukey RH, Veronese ME, Birkett DJ
Biochem Pharmacol 1996 Apr 26;51(8):1003-1008

OLANZAPINE
Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia. [ PMID 15545309 ]
Chiu CC, Lane HY, Huang MC, Liu HC, Jann MW, Hon YY, Chang WH, Lu ML.
J Clin Pharmacol. 2004 Dec;44(12):1385-90.

ONDANSETRON (in part)
Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. [ PMID 8591723 ]
Dixon CM, Colthup PV, Serabjit-Singh CJ, Kerr BM, Boehlert CC, Park GR, Tarbit MH
Drug Metab Dispos 1995 Nov;23(11):1225-1230

PHENACETIN
Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. [ PMID 8474022 ]
Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO.
J Pharmacol Exp Ther 1993 Apr;265(1):401-407.

Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. [ PMID 19219744 ]
Laine JE, Auriola S, Pasanen M, Juvonen RO.
Xenobiotica. 2009 Jan;39(1):11-21.

PROPRANOLOL
Selective induction of propranolol metabolism by smoking: Additional effects on renal clearance of metabolites. [ PMID 3598909 ]
Walle, U.K., Walle, T., Cowart, T.D., Conradi, E.C., and Gaffney, T.E.
J. of Pharm. & Exp. Ther. 241:928-933, 1987.

Fluvoxamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. [ PMID 3096686 ]
Benfield, P and Ward A
Drugs 1986;32:313-334
[Fluvoxamine is a potent inhibitor of propranolol metabolism in vivo.]

RILUZOLE
Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. [ PMID 9316860 ]
Sanderink GJ, Bournique B, Stevens J, Petry M, Martinet M
J Pharmacol Exp Ther 1997 Sep;282(3):1465-1472

ROPIVACAINE
Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: an interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. [ PMID 9834040 ]
Arlander E, Ekstrom G, Alm C, Carrillo JA, Bielenstein M, Bottiger Y, Bertilsson L, Gustafsson LL
Clin Pharmacol Ther 1998 Nov;64(5):484-91

TACRINE
Determination of human hepatic cytochrome P450 1A2 activity in vitro: use of tacrine as an isozyme-specific probe. [ PMID 8565783 ]
Spaldin V, Madden S, Adams DA, Edwards RJ, Davies DS, Park BK
Drug Metab Dispos 1995;23(9):929-934

THEOPHYLLINE
Metabolism of theophylline by cDNA-expressed human cytochromes P450. [ PMID 7619675 ]
Ha HR, Chen J, Freiburghaus AU, Follath F
Br J Clin Pharmacol 1995;39:321-326

TIZANIDINE
Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. [ PMID 15592331 ]
Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ.
Clin Pharmacol Ther. 2004 Dec;76(6):598-606

Fluvoxamine drastically increases concentrations and effects of tizanidine: a potentially hazardous interaction. [ PMID 15060511 ]
Granfors MT, Backman JT, Neuvonen M, Ahonen J, Neuvonen PJ.
Clin Pharmacol Ther. 2004 Apr;75(4):331-41

VERAPAMIL
The effect of three different oral doses of verapamil on the disposition of theophylline. [ PMID 1505606 ]
Stringer KA, Mallet J, Clarke M, Lindenfeld JA
Eur J Clin Pharmacol 1992;43(1):35-38

Verapamil-induced inhibition of theophylline elimination in healthy humans. [ PMID 2315261 ]
Nielsen-Kudsk JE, Buhl JS, Johannessen AC
Pharmacol Toxicol 1990 Feb;66(2):101-103

WARFARIN
Possible antiretroviral therapy-warfarin drug interaction. [ PMID 18576910 ]
Fulco PP, Zingone MM, Higginson RT.
Pharmacotherapy. 2008 Jul;28(7):945-9.

ZILEUTON
Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its N-dehydroxylated metabolite, Abbott-66193. [ PMID 8654206 ]
Machinist JM, Mayer MD, Shet MS, Ferrero JL, Rodrigues AD
Drug Metab Dispos. 1995 Oct; 23(10): 1163-1174

ZOLMITRIPTAN
Determination of the human cytochrome P450 isoforms involved in the metabolism of zolmitriptan. [ PMID 10553725 ]
Wild MJ, McKillop D, Butters CJ
Xenobiotica. 1999 Aug;29(8):847-57
 

 1A2 INHIBITORS: 

AMIODARONE
Inhibitory effects of antiarrhythmic drugs on phenacetin O-deethylation catalysed by human CYP1A2. [ PMID 9578183 ]
Kobayashi K, Nakajima M, Chiba K, Yamamoto T, Tani M, Ishizaki T, Kuroiwa Y.
Br J Clin Pharmacol 1998 Apr;45(4):361-368.

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.

Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. [ PMID 10223772 ]
Martínez C, Albet C, Agúndez JA, Herrero E, Carrillo JA, Márquez M, Benítez J, Ortiz JA.
Clin Pharmacol Ther. 1999 Apr;65(4):369-76.

Imipramine-cimetidine interaction: impairment of clearance and enhanced absolute bioavailability. [ PMID 6726654 ]
Abernethy DR, Greenblatt DJ, Shader RI.
J Pharmacol Exp Ther. 1984 Jun;229(3):702-5.

CIPROFLOXACIN
Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. [ PMID 15592331 ]
Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ.
Clin Pharmacol Ther. 2004 Dec;76(6):598-606.

FLUOROQUINOLONES
The effect of ciprofloxacin on theophylline pharmacokinetics in healthy subjects. [ PMID 7619673 ]
Batty K, Davis TME, Ilett KF, Dusci LJ, Langton SR.
Br J Clin Pharmacol 1995;39(3):305-311.

FLUVOXAMINE
Fluvoxamine is a potent inhibitor of cytochrome P4501A2. [ PMID 8466541 ]
Brosen K, Skjelbo E, Rasmussen BB, Poulsen HE, Loft S.
Biochem Pharmacol 1993 Mar 24;45(6):1211-1214.

Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism; comparative studies with selected SSRIs, and effects on human hepatic CYP3A4, CYP2C9 and CYP1A2. [ PMID 9205822 ]
Ball SE, Ahern D, Scatina J, Kao J.
Br J Clin Pharmacol. 1997 Jun;43(6):619-26.

Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia. [ PMID 15545309 ]
Chiu CC, Lane HY, Huang MC, Liu HC, Jann MW, Hon YY, Chang WH, Lu ML.
J Clin Pharmacol. 2004 Dec;44(12):1385-90.

Cytochrome P450 1A2 is a major determinant of lidocaine metabolism in vivo: effects of liver function. [ PMID 14749694 ]
Orlando R, Piccoli P, De Martin S, Padrini R, Floreani M, Palatini P.
Clin Pharmacol Ther. 2004 Jan;75(1):80-8.

Fluvoxamine-theophylline interaction: gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2. [ PMID 11719727 ]
Yao C, Kunze KL, Kharasch ED, Wang Y, Trager WF, Ragueneau I, Levy RH.
Clin Pharmacol Ther. 2001 Nov;70(5):415-24.

Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men. [ PMID 11240973 ]
Kusumoto M, Ueno K, Oda A, Takeda K, Mashimo K, Takaya K, Fujimura Y, Nishihori T, Tanaka K.
Clin Pharmacol Ther. 2001 Mar;69(3):104-7.

Fluvoxamine is a potent inhibitor of tacrine metabolism in vivo. [ PMID 10456487 ]
Larsen JT, Hansen LL, Spigset O, Brøsen K.
Eur J Clin Pharmacol. 1999 Jul;55(5):375-82.

Influence of the CYP1A2 inhibitor fluvoxamine on tacrine pharmacokinetics in humans. [ PMID 9209244 ]
Becquemont L, Ragueneau I, Le Bot MA, Riche C, Funck-Brentano C, Jaillon P.
Clin Pharmacol Ther. 1997 Jun;61(6):619-27.

FURAFYLLINE
Furafylline is a potent and selective inhibitor of P4501A2 in man. [ PMID 2378786 ]
Sesardic D, Boobis AR, Murray BP, Murray S, Segura J, de la Torre R, Davies DS.
Br J Clin Pharmacol 1990;29:651-663

INTERFERON
Regulation of hepatic cytochrome P-450 during infectious disease. [ PMID 1695539 ]
Renton KW, Knickle LC
Can J Physiol Pharmacol 1990 Jun;68(6):777-781

METHOXSALEN
Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. [ PMID 8819299 ]
Ono S, Hatanaka T, Hotta H, Satoh T, Gonzalez FJ, Tsutsui M.
Xenobiotica. 1996 Jul;26(7):681-93.

MIBEFRADIL
Metabolism of the calcium antagonist, mibefradil (POSICOR,Ro40-5967). Part III. Comparative pharmacokinetics of mibefradil and its major metabolites in rat, marmoset, cynomolgus monkey and man. [ PMID 9211656 ]
Wiltshire HR, Sutton BM, Heeps G, Betty AM, Angus DW, Harris SR, Worth E, Welker HA
Xenobiotica 1997 Jun;27(6):557-571
 

 1A2 INDUCERS: 

BROCCOLI
Effects of dietary broccoli on human in vivo caffeine metabolism: a pilot study on a group of Jordanian volunteers. [ PMID 17266520 ]
Hakooz N, Hamdan I.
Curr Drug Metab. 2007 Jan;8(1):9-15.

BRUSSEL SPROUTS
3,3-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. [ PMID 9741959 ]
Lake BG, Tredger JM, Renwick AB, Barton PT, Price RJ. Xenobiotica. 1998 Aug;28(8):803-11.

CHARGRILLED MEAT
Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers. [ PMID 10381914 ]
Fontana RJ, Lown KS, Paine MF, Fortlage L, Santella RM, Felton JS, Knize MG, Greenberg A, Watkins PB
Gastroenterology 1999 Jul;117(1):89-98

INSULIN
Hyperinsulinemia causes a preferential increase in hepatic P4501A2 activity. [ PMID 1562279 ]
Barnett CR, Wilson J, Wolf CR, Flatt PR, Ioannides C
Biochem Pharmacol 1992;43(6):1255-61

METHYLCHOLANTHRENE
3-Methylcholanthrene and pyridine effects on CYP1A1 and CYP1A2 expression in rat renal tissue. [ PMID 7493548 ]
H Kim, S Reddy, RF Novak
Drug Metab Dispos. 1995 Aug;23(8):818-24.

Induction of CYP1A1, but not CYP1A2, in adrenals of 3, 3'-methylcholanthrene-treated guinea pigs. [ PMID 9637727]
Black VH, Wang AF, Henry M, Shaw PM.
Arch Biochem Biophys. 1998 Jun 15;354(2):197-205.

MODAFINIL
In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. [ PMID 10820139 ]
Robertson P, DeCory HH, Madan A, Parkinson A.
Drug Metab Dispos 2000 Jun;28(6):664-71

NAFCILLIN
Interaction between warfarin and nafcillin: case report and review of the literature. [ PMID 10820139 ]
Kim KY, Frey RJ, Epplen K, Foruhari F.
Pharmacotherapy. 2007 Oct;27(10):1467-70.

BETA-NAPHTHOFLAVONE
Involvement of the CYP1A Subfamily in Stereoselective Metabolism of Carvedilol in beta-Naphthoflavone-Treated Caco-2 Cells. [ PMID 19252307 ]
Ishida K, Taguchi M, Akao T, Hashimoto Y.
Biol Pharm Bull. 2009 Mar;32(3):513-6.

OMEPRAZOLE
Increase of cytochrome P450IA2 activity by omeprazole: evidence by the 13C-[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. [ PMID 1505152 ]
Rost KL, Brösicke H, Brockmöller J, Scheffler M, Helge H, Roots I.
Clin Pharmacol Ther. 1992 Aug;52(2):170-80.

TOBACCO
Effect of smoking on caffeine clearance. [ PMID 657717 ]
Parsons WD, Neims AH.
Clin pharmacol Ther 1978;24(1):40-45

Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test. [ PMID 6800827 ]
Wietholz H, Voegelin M, Arnaud MJ, Bircher J, Preisig R
Eur J Clin Pharmacol 1981;21:53-59