Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-10-16
2000-12-12
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
549282, A61K 31352, C07D49306
Patent
active
061600067
ABSTRACT:
The present invention provides a composition and methods for inhibiting cytochrome P450 enzyme activity and in particular, inhibiting the activity of the cytochrome P450 3A sub-family of enzymes, specifically, CYP3A4. The present invention provides 6',7'-dihydroxybergamottin, a furanocoumarin, as the compound primarily responsible for the inhibitory effects of grapefruit juice on cytochrome P450 enzyme activity. The present invention also provides a novel synthesis scheme for 6',7'-dihydroxybergamottin.
REFERENCES:
Bailey, D.G. et al., "Grapefruit juice-felodipine interaction: Mechanism, predictability, and effect of naringin," Clin. Pharmacol. Ther. 53(6):637-642 (1993).
Bailey, D.G. et al. "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics," Clin. Pharmacol. Ther. 54(6):589-594 (1993).
Bailey, D.G. et al., "Interaction of citrus juices with felodipine and nifedipine," Lancet 337:268-269 (1991).
Benton, R. et al., "Grapefruit Juice Alters Terfenadine Pharmacokinetics Resulting In Prolongation Of QTc," Clin. Pharmacol. Ther. 55:146 (1994).
Block, G. et al., "Fruit, Vegetables, and Cancer Prevention: A Review of the Epidemiological Evidence," Nutri. Cancer 18:1-29 (1992).
Brian, W.R. et al., "Catalytic Activities of Human Liver Cytochrome P-450 IIIA4 Expressed in Saccharomyces cerevisiae," Biochem. 29:11280-11292 (1990).
Burke, M.D. et al., "Ethoxy-, Pentoxy- And Benzyloxyphenoxazones And Homologues: A Series Of Substrates To Distinguish Between Different Induced Cytochromes P450," Biochem. Pharmacol. 34:3337-3345 (1985).
Chadwick, R.W. et al., "Role Of The Gastrointestinal Mucosa And Microflora In The Bioactivation Of Dietary And Environmental Mutagens Or Carcinogens," Drug Metab. Rev. 24:425-492 (1992).
Chatterjee, A. et al., "The Synthesis Of Bergamottin," J. Chem. Soc. 428:2246-2247 (1961).
Corcoran, G.B. et al., "Effects of N-Acetylcysteine on the Disposition and Metabolism of Acetaminophen in Mice," J. Pharmcol. Exp. Ther. 232:857-863 (1985).
Cornish-Bowden, A., "A Simple Graphical Method for Determining the Inhibition Constants of Mixed, Uncompetitive and Non-Competitive Inhibitors," Biochem. J. 137:143-144 (1974).
Dixon, M., "The Determination of Enzyme Inhibitor Constants," Biochem. J. 55:170-171 (1953).
Dreyer, D.L. et al., "Coumarins Of Citrus Macroptera," Phytochemistry 12:3011-3013 (1973).
Ducharme, M.P. et al., "Trough concentrations of cyclosporine in blood following administration with grapefruit juice," Br. J. Clin. Pharmacol. 36:457-459 (1993).
Ducharme M.P. et al., "Disposition of intravenous and oral cyclosporine after administration with grapefruit juice," Clin. Pharmacol. Ther. 57:485-491 (1995).
Edwards, D.J. et al., "Identification Of 6',7'-Dihydroxybergamottin, A Cytochrome P450 Inhibitor, In Grapefruit Juice," Drug Metab. Dispos. 24:1287-1290 (1996).
Edwards, D.J. et al., "Naringin And Naringenin Are Not The Primary CYP3A Inhibitors In Grapefruit Juice," Life Sciences 59:1025-1030 (1996).
Ferguson, L.R., "Antimutagens as cancer chemopreventive agents in the diet," Mutat. Res. 307:395-410 (1994).
Fouin-Fortunet, H. et al., "Inactivation of Cytochrome P-450 by the Drug Methoxsalen," J. Pharmacol. Exp. Ther. 236:237-247 (1986).
Fuhr, U. et al., "Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man," Br. J. Clin. Pharmacol. 35:431-436 (1993).
Gonzalez, F.J. et al., "Role Of Human Cytochromes P450 In The Metabolic Activation Of Chemical Carcinogens And Toxins," Drug Metab. Rev. 26:165-183 (1994).
Greenlee, W.F. et al., "An Improved Assay Of 7-Ethoxycoumarin Odeethylase Activity: Induction Of Hepatic Enzyme Activity In C57BL/6J And DBA/2J Mice By Phenobarbital, -3-Methylcholanthrene And 2,3,7,8-Tetrachlorodibenzo-p-Dioxin," J. Pharmacol. Exp. Ther. 205:596-605 (1978).
Greenwald, P. et al., "New Directions In Dietary Studies In Cancer: The National Cancer Institute," Adv. Exp. Med. Biol. 369:229-239 (1995).
Guengerich, F.P. et al., "In vitro inhibition of dihydropyridine oxidation and aflatoxin B.sub.1 activation in human liver microsomes by naringenin and other flavonoids," Carcinogenesis 11:2275-2279 (1990).
Guengerich, F.P., "Roles of Cytochrome P-450 Enzymes in Chemical Carcinogenesis and Cancer Chemotherapy," Cancer Res. 48:2946-2954 (1988).
Habig, W.H. et al., "Glutathione S-Transferases," J. Biol. Chem. 249:7130-7139 (1974).
Hebert, M.F. et al., "Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction," Clin. Pharmacol. Ther. 52:453-457 (1992).
Hertog, M.G.L. et al., "Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study," Lancet 342:1007-1011 (1993).
Hukkinen, S.K. et al., "Pharmacokinetics And Drug Disposition--Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice," Clin. Pharmacol. Ther. 58:127-131 (1995).
Keogh, A. et al., "Ketoconazole To Reduce The Need For Cyclosporine After Cardiac Transplantation," N. Engl. J. Med. 333:628-633 (1995).
Kimura, R.E. et al., "Portal Venous and Aortic Glucose and Lactate Changes in a Chronically Catheterized Rat," Pediatr.Res. 23:235-240 (1988).
Kronbach, T. et al., "Cyclosporine metabolism in human liver: Identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs," Clin. Pharmac. Ther. 43:630-635 (1988).
Kupferschmidt, H.H.T. et al., "Interaction between grapefruit juice and midazolam in humans," Clin. Pharmacol. Ther. 58(1):20-28 (1995).
Lin, J.H., "Species Similarities And Differences In Pharmacokinetics," Drug Metab. Dispos. 23:1008-1021 (1995).
Lundahl, J. et al., "Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects," Eur. J. Clin. Pharmacol. 49:61-67 (1995).
Mays, D.C. et al., "Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans," Clin. Pharmacol. Ther. 42(6):621-626 (1987).
Merkel, U. et al., "Grapefruit juice inhibits 7-hydroxylation of coumarin in healthy volunteers," Eur. J. Clin. Pharmacol. 46:175-177 (1994).
Miniscalco, A. et al., "Inhibition of Dihydropyridine Metabolism in Rat and Human Liver Microsomes by Flavonoids Found in Grapefruit Juice," J. Pharmacol. Exp. Ther. 261(3):1195-1199 (1992).
Olkkola, K.T. et al., "A potentially hazardous interaction between erythromycin and midazolam," Clin. Pharmacol. Ther. 53:298-305 (1993).
Peter, R. et al., "Hydroxylation of Chlorzoxazone as a Specific Probe for Human Liver Cytochrome P-450IIE1," Chem. Res. Toxicol. 3:566-573 (1990).
Raftogianis, R.B. et al., "Effect of Lipid-Free Total Parenteral Nutrition on Hepatic Drug Conjugation in Rats," J. Pharmacol. Exp. Ther. 276:602-608 (1996).
Rashid, J. et al., "Quercetin, an in vitro inhibitors of CYP3A, does not contribute to the interaction between nifedipine and grapefruit juice," Br. J. Clin. Pharmacol. 36:460-463 (1993).
Ritter, J.K. et al., "Induction And Inhibition Of Rat Hepatic Drug Metabolism By N-Substituted Imidazole Drugs," Drug Metab. Dispos. 15(3):335-343 (1987).
Schonberg, A. et al., "Furo-chromones and -Coumarins (X): On the Constitution of Prangenin," J. Am. Chem. Soc. 77:2563-2564 (1955).
Shimada T. et al., "Evidence for cytochrome P-450.sub.NF, the nifedipine oxidase, being the principal enzyme involved in the bioactivation of aflatoxins in human liver," Proc. Natl. Acad. Sci. USA 86(1):462-465 (1989).
Shimada, T. et al., "Interindividual Variations in Human Liver Cytochrome P-450 Enzymes Involved in the Oxidation of Drugs, Carcinogens and Toxic Chemicals: Studies with Liver Microsomes of 30 Japanese and 30 Caucasians," J. Pharmacol. Exp. Ther. 270(1):414-423 (1994).
Siess, M.-H. et al., "Heterogenous Effects of Natural Flavonoids on Monooxygenase Activities in Human and Rat Liver Microsomes," Toxicol. Appl. Pharmacol. 130:73-78 (1995).
Sonderfan, A.J. et al., "Regulation of Testosterone Hydroxylation by Rat Liver Microsomal Cytochrome P-450
Edwards David J.
Woster Patrick M.
Richter Johann
Solola Taofiq A.
Wayne State University
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