Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: Opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (S)-fluoxetine, and N-desmethyldiltiazem

Drug Metabolism and Disposition

Volumn 38, Issue 6, 2010, Pages 963-972

  Hanson, Kelsey L ^a   VandenBrink, Brooke M ^a   Babu, Kantipudi N ^a   Allen, Kyle E ^a   Nelson, Wendel L ^a   Kunze, Kent L ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALIPHATIC AMINE; AMINE; CYTOCHROME P450 2C11; CYTOCHROME P450 2C19; CYTOCHROME P450 3A4; DESIPRAMINE; DRUG METABOLITE; FLUOXETINE; HYDROXYLAMINE; N HYDROXY N NORDILTIAZEM; N HYDROXYDESIPRAMINE; N HYDROXYFLUOXETINE; N METHYL D3 DESIPRAMINE; N NORDESIPRAMINE; N NORDILTIAZEM; N,N DINORDILTIAZEM; NORFLUOXETINE; UNCLASSIFIED DRUG;

ARTICLE; COMPETITIVE INHIBITION; DEALKYLATION; HUMAN; HYDROXYLATION; PRIORITY JOURNAL; REACTION ANALYSIS; REACTION TIME;

ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME SYSTEM; DESIPRAMINE; DILTIAZEM; FLUOXETINE; HUMANS; HYDROXYLAMINE; HYDROXYLAMINES; HYDROXYLATION; IMIPRAMINE; MICROSOMES, LIVER; OXIDOREDUCTASES, N-DEMETHYLATING; STEROID 16-ALPHA-HYDROXYLASE;

EID: 77952312729     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.110.032391     Document Type: Article

References (39)

1. Alexander J (1993) A convenient preparation of N-demethyldiltiazem and its conversion to a diltiazem homolog. Org Prep Proced Int 25:133-137.
2. Baba T, Yamada H, Oguri K, and Yoshimura H (1988) Participation of cytochrome P-450 isozymes in N-demethylation, N-hydroxylation and aromatic hydroxylation of methamphetamine. Xenobiotica 18:475-484.
3. Backman JT, Olkkola KT, Aranko K, Himberg JJ, and Neuvonen PJ (1994) Dose of midazolam should be reduced during diltiazem and verapamil treatments. Br J Clin Pharmacol 37:221-225. (Pubitemid 24212179)
4. Beckett AH and Haya K (1978) The stereoselective metabolism of ethylamphetamine with fortified rabbit liver homogenates. Xenobiotica 8:85-96.
5. Beckett AH, Hutt AJ, and Navas GE (1983) Metabolism of imipramine in vitro: synthesis and characterization of N-hydroxydesmethylimipramine. Xenobiotica 13:391-405. (Pubitemid 13023095)
6. Bensoussan C, Delaforge M, and Mansuy D (1995) Particular ability of cytochrome P450 3A to form inhibitory P450-iron-metabolite complexes upon metabolic oxidation of aminodrugs. Biochem Pharmacol 49:591-602.
7. Buening MK and Franklin MR (1976) The formation of cytochrome P-450-metabolic intermediate complexes in microsomal fractions from extrahepatic tissues of the rabbit. Drug Metab Dispos 4:556-561.
8. Cerny MA and Hanzlik RP (2005) Cyclopropylamine inactivation of cytochromes P450: role of metabolic intermediate complexes. Arch Biochem Biophys 436:265-275.
9. Chunsen L, Wei W, Kyung-Bin C, and Sason S (2009) Oxidation of tertiary amines by cytochrome P450 - kinetic isotope effect as a spin-state reactivity probe. Chem Eur J 15:8492-8503.
10. Corey EJ and Reichard GA (1989) Enantioselective and practical syntheses of R- and S-fluoxetines. Tetrahedron Lett 30:5207-5210.
11. Correia MA and Ortiz de Montellano PR (2005) Cytochrome P450: Structure, Mechanism, and Biochemistry, 3rd ed (Ortiz de Montellano PR ed) pp 263-267, Kluwer Academic/Plenum Publishers, New York.
12. Di Marco A, Cellucci A, Chaudhary A, Fonsi M, and Laufer R (2007) High-throughput radiometric CYP2C19 inhibition assay using tritiated (S)-mephenytoin. Drug Metab Dispos 35:1737-1743. (Pubitemid 47481564)
13. Duncan JD, Hallström G, Paulsen-Sörman U, Lindeke B, and Cho AK (1983) Effects of α-carbon substituents on the N-demethylation of N-methyl-2-phenethylamines by rat liver microsomes. Drug Metab Dispos 11:15-20. (Pubitemid 13180894)
14. Franklin MR (1974) The formation of a 455 nm complex during cytochrome P-450-dependent N-hydroxyamphetamine metabolism. Mol Pharm 10:975-985.
15. Franklin MR (1995) Enhanced rates of cytochrome P450 metabolic- intermediate complex formation from nonmacrolide amines in rifampicin-treated rabbit liver microsomes. Drug Metab Dispos 23:1379-1382.
16. Galetin A, Burt H, Gibbons L, and Houston JB (2006) Prediction of time-dependent CYP3A4 drug-drug interactions: impact of enzyme degradation, parallel elimination pathways, and intestinal inhibition. Drug Metab Dispos 34:166-175. (Pubitemid 43042658)
17. Gumbrecht JR and Franklin MR (1979) The formation of cytochrome P-450-metabolic intermediate complexes from amines, in the isolated perfused rat liver. Xenobiotica 9:547-554.
18. Hall J, Naranjo CA, Sproule BA, and Herrmann N (2003) Pharmacokinetic and pharmacodynamic evaluation of the inhibition of alprazolam by citalopram and fluoxetine. J Clin Psychopharmacol 23:349-357. (Pubitemid 36951176)
19. Hilborn JW, Lu Z-H, Jurgens AR, Fang QK, Byers P, Wald SA, and Senanayake CH (2001) A practical asymmetric synthesis of (R)-fluoxetine and its major metabolite (R)-norfluoxetine. Tetrahedon Lett 42:8919-8921.
20. Jeffery EH and Mannering GJ (1983) Interaction of constitutive and phenobarbital-induced cytochrome P-450 isozymes during the sequential oxidation of benzphetamine. Explanation for the difference in benzphetamine-induced hydrogen peroxide production and 455-nm complex formation in microsomes from untreated and phenobarbital-treated rats. Mol Pharmacol 23:748-757.
21. Jönsson KH and Lindeke B (1992) Cytochrome P-455 nm complex formation in the metabolism of phenylalkylamines. XII. Enantioselectivity and temperature dependence in microsomes and reconstituted cytochrome P-450 systems from rat liver. Chirality 4:469-477.
22. Kamal A, Khanna GBR, and Ramu R (2002) Chemoenzymatic synthesis of both enantiomers of fluoxetine, tomoxetine and nisoxetine: lipase-catalyzed resolution of 3-aryl-3-hydroxypropanenitriles. Tetrahedron Asymm 13:2039-2051.
23. Kawalek JC, Levin W, Ryan D, and Lu AY (1976) Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds, and endogenous substrates. IX. The formation of a 455-nm metabolite-cytochrome P-450 complex. Drug Metab Dispos 4:190-194.
24. Kurebayashi H (1989) Kinetic deuterium isotope effects on deamination and N-hydroxylation of cyclohexylamine by rabbit liver microsomes. Arch Biochem Biophys 270:320-329.
25. Lindeke B, Paulsen U, and Anderson E (1979) Cytochrome P-455 complex formation in the metabolism of phenylalkylamines-IV. Spectral evidences for metabolic conversion of methamphetamine to N-hydroxyamphetamine. Biochem Pharmacol 28:3629-3635.
26. Lindeke B, Paulsen-Sörman U, Hallström G, Khuthier AH, Cho AK, and Kammerer RC (1982) Cytochrome P-455-nm complex formation in the metabolism of phenylalkylamines. VI. Structure-activity relationships in metabolic intermediary complex formation with a series of α-substituted 2-phenylethylamines and corresponding N-hydroxylamines. Drug Metab Dispos 10:700-705.
27. Liu Z and Franklin MR (1985) Cytochrome P-450 ligands: metyrapone revisited. Arch Biochem Biophys 241:397-402. (Pubitemid 15023268)
28. Mayhew BS, Jones DR, and Hall SD (2000) An in vitro model for predicting in vivo inhibition of cytochrome P450 3A4 by metabolic intermediate complex formation. Drug Metab Dispos 28:1031-1037.
29. McGinnity DF, Berry AJ, Kenny JR, Grime K, and Riley RJ (2006) Evaluation of timedependent cytochrome P450 inhibition using cultured human hepatocytes. Drug Metab Dispos 34:1291-1300.
30. Mitchell D and Koening TM (1995) Synthesis of R- and S- fluoxetine, norfluoxetine and related compounds from styrene oxide. Syn Commun 25:1231-1238.
31. O'Neil IA, Cleator E, and Tapolczay DJ (2001) A convenient synthesis of secondary hydroxylamines. Tetrahedron Lett 42:8247-8249.
32. Ohmori S, Ishii I, Kuriya S, Taniguchi T, Rikihisa T, Hirose S, Kanakubo Y, and Kitada M (1993) Effects of clarithromycin and its metabolites on the mixed function oxidase system in hepatic microsomes of rats. Drug Metab Dispos 21:358-363.
33. Polasek TM and Miners JO (2008) Time-dependent inhibition of human drug metabolizing cytochromes P450 by tricyclic antidepressants. Br J Clin Pharmacol 65:87-97.
34. Silverman RB (1988) Mechanism-Based Enzyme Inactivation: Chemistry and Enzymology, pp 1-30, CRC Press, Boca Raton, FL.
35. Zhang X, Galinsky RE, Kimura RE, Quinney SK, Jones DR, and Hall SD (2010) Inhibition of CYP3A by erythromycin: in vitro-in vivo correlation in rats. Drug Metab Dispos 38:61-72.
36. Zhang X, Jones DR, and Hall SD (2009a) Prediction of the effect of erythromycin, diltiazem, and their metabolites, alone and in combination, on CYP3A4 inhibition. Drug Metab Dispos 37:150-160.
37. Zhang X, Quinney SK, Gorski JC, Jones DR, and Hall SD (2009b) Semiphysiologically based pharmacokinetic models for the inhibition of midazolam clearance by diltiazem and its major metabolite. Drug Metab Dispos 37:1587-1597.
38. Zhao P, Kunze KL, and Lee CA (2005) Evaluation of time-dependent inactivation of CYP3A in cryopreserved human hepatocytes. Drug Metab Dispos 33:853-861.
39. Zhao P, Lee CA, and Kunze KL (2007) Sequential metabolism is responsible for diltiazem-induced time-dependent loss of CYP3A. Drug Metab Dispos 35:704-712.