TH55858A - A mixture of medications. - Google Patents

Abstract

DC60 (29/04/51) Invention concerning safe non-interacting drug combinations of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that is (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid or its pharmacologically acceptable salt (agent) with a drug that is an inducer, inhibitor, or cytochrome substrate. Specifically, cytochrome P450 isoenzyme 3A4 isoenzyme combinations are useful in the treatment of hyperlipidemia in humans receiving immunosuppressive chemotherapy. Popular combinations are agent and fibrate drug combinations. The use of these combinations in the treatment of hyperlipidemia in mammals and the development of drugs containing such combinations for this treatment are also discussed. An invention concerning safe non-interacting drug combinations of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl] isoenzyme 3A4 ... A combination of (methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid or its pharmacologically acceptable salt (agent) with a drug that is an inducer, inhibitor, or substrate of cytochrome P450, especially cytochrome P450 isoenzyme 3A4. Specific combinations are beneficial in the treatment of hyperlipidemia in humans receiving immunosuppressive chemotherapy. A popular combination is the agent and a fibrate drug. The use of this drug combination in the treatment of hyperlipidemia in mammals and the drugs containing such combinations for this treatment are discussed.

Claims (1)

1. A non-interacting drug combination consisting of an HMG-CoA reductase inhibitor (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhepte-6-enoic acid or its pharmacologically acceptable salt with a drug that is an inhibitor, inducer, or substrate of cytochrome P450 isoenzyme 3A4. 2. A non-interacting drug combination as claimed in claim 1 where the second drug is an inhibitor or inducer of P450 isoenzyme 3A4. 3. A non-interacting drug combination. 3. Non-interactive drug combination as claimed under claim 1 or 2. Here, each drug is administered concurrently or sequentially. 4. Non-interactive drug combination as claimed under any one of claim 1 through 3. Here, the second drug is used to lower cholesterol and is an inducer, inhibitor, or substrate of P450 isoenzyme 3A4. 5. Non-interactive drug combination as claimed under claim 4. Here, the second drug is selected from bezafibrate, clofibrate, fenofibrate, gemfibrozol, and niacin. 6. Non-interactive drug combination as claimed under claim 5. Here, the second drug is fenofibrate. 7. Non-interactive drug combination as claimed under claim 2. Any one of the claims 1 through 3 herein, the second drug is used in the treatment of coronary artery disease and is also an inhibitor, inducer, or substrate of P450 isoenzyme 3A4. 8. Non-interactive drug combination as claimed in claim 7 herein, the second drug is selected from digitoxin, diltiazem, losartan, nifedipine, quinidine, verapamil, and warfarin. 9. Non-interactive drug combination as claimed in any one of the claims 1 through 3 herein, the second drug is used in immunosuppression therapy and is also an inducer, inhibitor, or substrate of P450 isoenzyme 3A4. 10. Non-interactive drug combination. As claimed under claim 9, the second drug herein is chosen from cyclosporin, tacrolimus, and corticosteroid (page 2, none). 15. The pharmacological formulations claimed under claim 12 herein, the second drug is a P450 3A4 inducer including; carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, sulfadimidine, sulfinipyrazone, and thyroxylenedomycin. (triacetyloleandomycin) 16. A pharmacy pack containing the first drug, which is (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid or its pharmacologically acceptable salt. And the second drug is an inducer, inhibitor, or substrate of P450 isoenzyme 4A4. 17. The pharmacy pack referred to under claim 16 herein, the second drug is used to lower cholesterol and is an inducer, inhibitor, or substrate of P450 isoenzyme 3A4. 18. The pharmacy pack referred to under claim 17 herein, the second drug is selected from bezafibrate, clofibrate, fenofibrate, gemfibrozol, and niacin. 19. The pharmacy pack referred to under claim 16 herein, the second drug is used to treat coronary artery disease and is also an inhibitor. 20. The pharmacy pack referred to in claim 19 herein is a second drug selected from digitoxin, diltiazem, losartan, nifedipine, quinidine, verapamil, and warfarin. 21. The pharmacy pack referred to in claim 16 herein is a second drug, a substrate of P450 isoenzyme 3A4, selected from acetaminophen. (acetominophen) aldrin, aflentanil, amiodorane, astemizole, benzphetamine, budenoside, carbamazepine, cyclophosphamide, cyclosporin, dapsone, digitoxin, ditiazem, diazepam, erthromycin, etoposide, flutamide, hydroxyarginine (hydroxyarginine) ifosphamide, imipramine, lansoprazole, lidocaine, lovatidine, losartan, lovastatin, midrazolam, nifedipine, omerprazole, quinindine, rapamycin, retenoic acid, steroids, tacrolimus, teniposide, theophyline, toremifene, traizolam, trolinedomycin (troleandomycin), verapamil, warfarin, zatosetron, and zonisamide. 22. The pharmacy pack referred to under claim 16 herein is the second drug, which is an inhibitor of P450 isoenzyme 3A4 and is selected from clotrimazole, ethinylestradiol, gestodene, itraconazole, ketoconazole, miconazole, diltiazem, naringenin, erthromycin, cyclosporin, and triacetiolinemycin. (triacetyloleandomycin) 23. The pharmacy pack referred to under claim 16 herein is the second drug of which is a P450 3A4 inhibitor and is selected from carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, sulfadimidine, sulfinipyrazone and triacetyloleandomycin. 24. Use of (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-il](3R, 5S)-3,5-dihydroxyhept-6-enoic acid or its pharmacologically acceptable salts in drug preparations for use in combination with a second drug which is an inducer, inhibitor, or substrate of P450 isoenzyme 3A4. 25. The use of (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-il](3R, 5S)-3,5-dihydroxyhept-6-enoic acid or its pharmacologically acceptable salts in drug preparations for use in cholesterol-lowering therapy in combination with a second drug which 26. The use under claim 25 herein is an inducer, inhibitor, or substrate of cytochrome P450 isoenzyme 3A4. 27. The use under claim 25 herein is an inducer, inhibitor, or substrate of bezafibrate, clofibrate, fenofibrate, gemfibrozol, and niacin. 28. The use of (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhepto-6-enoic acid or its pharmacologically acceptable salts in drug preparations for the treatment of coronary artery disease in combination with a second drug that is an inhibitor. 28. Inducer or substrate of cytochrome P450 isoenzyme 3A4. 29. The use under claim 27 herein is a second drug chosen from digitoxin, diltiazem, losartan, nifedipine, quinidine, verapamil, and warfarin. 21. Use of (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid or its pharmacologically acceptable salt in drug preparations for use in Cholesterol-lowering treatment in patients receiving immunosuppressive therapy 30. The claimed use under claim 29 herein is immunosuppressive therapy comprising cyclosporin, tacrolimus, and corticosteroids. 31. The use of (E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R, 5S)-3,5-dihydroxyhepto-6-enoic acid or its pharmacologically acceptable salt in the formulation of a drug for therapeutic use in combination with a second drug of choice from besafibrate. (bezafibrate), clofibrate, fenofibrate, gemfibrozol, and niacin in patients receiving immunosuppressive therapy. 32. The claimed use under claim 31 herein is immunosuppressive therapy comprising the administration of a drug of choice: cyclosporin, tacrolimus, and corticosteroid.