Involvement of CYP3A4/5 and CYP2D6 in the metabolism of aconitine using human liver microsomes and recombinant CYP450 enzymes

Toxicology Letters

Volumn 202, Issue 1, 2011, Pages 47-54

  Tang, Lan ^a   Ye, Ling ^a   Lv, Chang ^a   Zheng, Zhijie ^a   Gong, Yun ^a   Liu, Zhongqiu ^a  

^a SOUTHERN MEDICAL UNIVERSITY   (China)

Author keywords

Aconitine; Cytochrome P450; LC MS MS; Metabolism; Microsomes

Indexed keywords

ACONITINE; AMIODARONE; CYTOCHROME P450 1A2; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 2E1; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; DIETHYLDITHIOCARBAMIC ACID; FLUVOXAMINE MALEATE; GEMFIBROZIL; KETOCONAZOLE; OMEPRAZOLE; QUINIDINE;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DEHYDROGENATION; DEMETHYLATION; HUMAN; HUMAN CELL; HYDROXYLATION; IN VITRO STUDY; LIQUID CHROMATOGRAPHY; LIVER MICROSOME METABOLISM; MASS SPECTROMETRY; PRIORITY JOURNAL; TANDEM MASS SPECTROMETRY;

ACONITINE; ADJUVANTS, IMMUNOLOGIC; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; HUMANS; MICROSOMES, LIVER; RECOMBINANT PROTEINS;

ACONITUM;

EID: 79952040477     PISSN: 03784274     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.toxlet.2011.01.019     Document Type: Article

References (25)

1. Ameri A. The effects of Aconitum alkaloids on the central nervous system. Prog. Neurobiol. 1998, 56:211-235.
2. Ando Y., Fuse E., Figg W.D. Thalidomide metabolism by the CYP2C subfamily. Clin. Cancer Res. 2002, 8:1964-1973.
3. Bachmann K.A., Ghosh R. The use of in vitro methods to predict in vivo pharmacokinetics and drug interactions. Curr. Drug Metab. 2001, 2:299-314.
4. Catterall W.A. Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Annu. Rev. Pharmacol. Toxicol. 1980, 20:15-43.
5. Chan T.Y., Tomlinson B., Critchley J.A., Cockram C.S. Herb-induced aconitine poisoning presenting as tetraplegia. Vet. Hum. Toxicol. 1994, 36:133-134.
6. Chan T.Y., Tomlinson B., Tse L.K., Chan J.C., Chan W.W., Critchley J.A. Aconitine poisoning due to Chinese herbal medicines: a review. Vet. Hum. Toxicol. 1994, 36:452-455.
7. Dresser G.K., Spence J.D., Bailey D.G. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin. Pharmacokinet. 2000, 38:41-57.
8. Eagling V.A., Tjia J.F., Back D.J. Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br. J. Clin. Pharmacol. 1998, 45:107-114.
9. FDA Guidance For Industry: Drug Metablism/Drug Interaction Studies In The Drug Development Process: Studies In Vitro 2006.
10. Gueorguieva I., Jackson K., Wrighton S.A., Sinha V.P., Chien J.Y. Desipramine, substrate for CYP2D6 activity: population pharmacokinetic model and design elements of drug-drug interaction trials. Br. J. Clin. Pharmacol. 2010, 70:523-536.
11. Hu M., Krausz K., Chen J., Ge X., Li J., Gelboin H.L., Gonzalez F.J. Identification of CYP1A2 as the main isoform for the phase I hydroxylated metabolism of genistein and a prodrug converting enzyme of methylated isoflavones. Drug Metab. Dispos. 2003, 31:924-931.
12. Kaneko R., Hattori S., Furuta S., Hamajima M., Hirata Y., Watanabe K., Seno H., Ishii A. Sensitive analysis of aconitine, hypaconitine, mesaconitine and jesaconitine in human body fluids and Aconitum tubers by LC/ESI-TOF-MS. J. Mass Spectrom. 2006, 41:810-814.
13. Kobayashi K., Urashima K., Shimada N., Chiba K. Selectivities of human cytochrome P450 inhibitors toward rat P450 isoforms: study with cDNA-expressed systems of the rat. Drug Metab. Dispos. 2003, 31:833-836.
14. Kolev S.T., Leman P., Kite G.C., Stevenson P.C., Shaw D., Murray V.S. Toxicity following accidental ingestion of Aconitum containing Chinese remedy. Hum. Exp. Toxicol. 1996, 15:839-842.
15. Li A.P., Kaminski D.L., Rasmussen A. Substrates of human hepatic cytochrome P450 3A4. Toxicology 1995, 104:1-8.
16. Murayama M., Mori T., Bando H., Amiya T. Studies on the constituents of Aconitum species IX. The pharmacological properties of pyro-type aconitine alkaloids, components of processed aconite powder 'kako-bushi-matsu': analgesic, antiinflammatory and acute toxic activities. J. Ethnopharmacol. 1991, 35:159-164.
17. Ohta H., Seto Y., Tsunoda N. Determination of Aconitum alkaloids in blood and urine samples I. High-performance liquid chromatographic separation, solid-phase extraction and mass spectrometric confirmation. J. Chromatogr. B: Biomed. Sci. Appl. 1997, 691:351-356.
18. Ohta H., Seto Y., Tsunoda N., Takahashi Y., Matsuura K., Ogasawara K. Determination of Aconitum alkaloids in blood and urine samples II. Capillary liquid chromatographic-frit fast atom bombardment mass spectrometric analysis. J. Chromatogr. B: Biomed. Sci. Appl. 1998, 714:215-221.
19. Quintieri L., Geroni C., Fantin M., Battaglia R., Rosato A., Speed W., Zanovello P., Floreani M. Formation and antitumor activity of PNU-159682, a major metabolite of nemorubicin in human liver microsomes. Clin. Cancer Res. 2005, 11:1608-1617.
20. Shu H., Yi-Ming W., Xu L.P., Miao C.Y., Su D.F. Increased susceptibility of ventricular arrhythmias to aconitine in anaesthetized rats is attributed to the inhibition of baroreflex. Clin. Exp. Pharmacol. Physiol. 2004, 31:249-253.
21. Sunying, Zhanghong-gui, Zhongda-fang, Zhanghan-qi Study on Metabolites of Aconitum Alkaloids in Human Urine. J. Chin. Pharm. Sci. 2003, 12.
22. Tanaka E. Clinically important pharmacokinetic drug-drug interactions: role of cytochrome P450 enzymes. J. Clin. Pharm. Ther. 1998, 23:403-416.
23. Wang Y., Wang S., Liu Y., Yan L., Dou G., Gao Y. Characterization of metabolites and cytochrome P450 isoforms involved in the microsomal metabolism of aconitine. J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 2006, 844:292-300.
24. Zhang H.G., Sun Y., Duan M.Y., Chen Y.J., Zhong D.F., Zhang H.Q. Separation and identification of Aconitum alkaloids and their metabolites in human urine. Toxicon 2005, 46:500-506.
25. Zhou Y.P., Liu W.H., Zeng G.Y., Chen D.H., Li H.Y., Song W.L. The toxicity of aconitine and its analogs and their effects on cardiac contractile function. Yao Xue Xue Bao 1984, 19:641-646.