Induction and inhibition of cytochrome P450-catalysed reduction of biologically active benfluron N-oxide

Drug Metabolism and Drug Interactions

Volumn 14, Issue 4, 1998, Pages 221-233

  Skalova L ^a   Nobilis, M ^b   Szotakova B ^a   Wsol V ^a   Kvasnickova E ^a  

^a Charles University in Prague Faculty of Pharmacy   (Czech Republic)

^b INSTITUTE OF MATHEMATICS   (Czech Republic)

Author keywords

Benfluron; Benfluron N oxide; Cytochrome P450 reductase activity; Cytostatic drugs; Microsomal reduction; N oxides

Indexed keywords

BENFLURON; BENFLURON N OXIDE; CYTOCHROME P450 REDUCTASE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BIOTRANSFORMATION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG METABOLISM; ENZYME ACTIVATION; ENZYME INHIBITION; MALE; METABOLISM; NONHUMAN; OXIDATION REDUCTION POTENTIAL; RAT; REDUCTION;

EID: 0031830022     PISSN: 07925077     EISSN: None     Source Type: Journal    
DOI: 10.1515/DMDI.1998.14.4.221     Document Type: Article

References (17)

1. Goeptar RA, Scheerens H, Vermeulen NPE. Oxygen and xenobiotic reductase activities of cytochrome P450. Crit Rev Toxicol 1995; 25: 25-65.
2. Wislocki PG, Miwa GT, Lu AYH. Reactions catalyzed by cytochrome P450 system. In: Jakoby WB, ed. Enzymatic Basis of Detoxication. London: Academic Press, 1980.
3. Testa B. Reduction catalyzed by cytochrome P450 and other oxidoreductases, In: Testa B, Caldwell J, eds. The Metabolism of Drugs and Other Xenobiotics. Biochemistry of Redox Reactions. London: Academic Press, 1995; 398-447.
4. Pfeifer S. Biotransformation von Arzneimitteln. Berlin: Veb Verlag und Gesundheit, 1975.
5. Patterson AV, Barham HM, Chinje EC, Adams GE, Harris AL, Stratford IJ. Importance of P450 reductase activity in determining sensitivity of breast tumour cells to the bioreductive drug, tirapazamine (SR 4233). Br J Cancer 1995; 72: 1144-1150.
6. Raffa RB, Haslego ML, Maryanoff CA, Villani FJ, Codd EE, Connelly CD, Martinez RP, Schupsky JJ, Buben JA, Wu VN, Takacs AN, Mckown LA. Unexpected antinociceptive effect of the N-oxide (RWJ 38705) of tramadol hydrochloride. J. Pharmacol Exp Ther 1996; 278; 1098-1104.
7. Kvasničková E, Nobilis M, Hais IM Chromatographic characterization of in vitro metabolites of 5[2-(N,N-dimethylamino)ethoxy]-7-oxo-7H-benzo[c]-fluorene. J Chromatogr 1984; 295: 201-209.
8. Nobilis M, Kvasničková E, Šroler A, Hais IM. Elimination of benflurone and its metabolites in the faeces and urine of rats. Drug Metab Drug Interact 1991; 9: 225-240.
9. Kvasničková E, Hais IM, Nobilis M. Relationship between NADPH and NADPH as cosubstrates of N-oxidation of the cytostatic benfluron by FMO. Prog Pharmacol Clin Toxicol 1991; 8: 137-146.
10. Vančurová I, et al. Patent application No. PCT/CS88/239413.
11. Skálová L, Nobilis M, Szotáková B, Trejtnar F, Kvasničková E. In vitro and in vivo biotransformation of benflurone N-oxide, a biologically active metabolite of a potential cytostatic. Exp Toxic Pathol 1996; 48: 366-370.
12. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin C phenol reagent. J Biol Chem 1951; 193: 165-275.
13. Omura T, Sato R. The carbon-monoxide-binding pigment of liver microsomes. II. Solubilization, purification, properties. J Biol Chem 1964; 239: 2379-2385.
14. Gram TE, Rogers LA, Fouts JR. Further studies on the metabolism of drugs by subfractions of hepatic microsomes. J Pharmacol Exp Ther 1967; 150: 479-493.
15. Lubet RA, Mayer RT, Cameron JW, Nims RW, Burcke MD, Wolf T, Guengerich FP. Dealkylation of penthoxyresorufin: a rapid and sensitive assay for measurig induction of cytochromes P450 by phenobarbital and other xenobiotics in the rat. Arch Biochem Biophys 1985; 83: 43-48.
16. Nobilis M, Anzenbacher P, Pastera J, Svoboda Z, Hrubý K, Květina J, Ubik K, Trejtnar F. Study of biotransformation of a potential benzo[c]fluorene antineoplastic using HPLC with high-speed-scanning UV detection. J Chromatogr B 1996; 681: 143-151.
17. Luu-The V, Cumps J, Dumont P. Metyrapone-reduced cytochrome P450 complex - a specific method for determination of phenobarbital inducible form of rat hepatic microsomal cytochrome P-450. Biochem Biophys Res Comm 1980; 93: 776-781.