Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4
The invention concerns safe non-interacting drug combinations of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, which is (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)a- mino]pyrimidin-5-yl](3R,5S)-3,5 -dihydroxyhept-6-enoic acid or a pharmaceutically acceptable salt thereof (the Agent) and a drug which is either an inducer, inhibitor or a substrate of cytochrome P450, in particular cytochrome P450 isoenzyme 3A4. Particular combinations are useful in treating hyperlipidaemia in humans who are receiving immunosuppressive chemotherapy. A preferred combination is the Agent and a fibrate drug, the use of such a combination in treating hyperlipidaemia in mammals, and medicaments containing such a combination for use in such treatments.
The invention relates to crystalline salts of the compound (E)-7-[4-(4-fluorophenyl)isopropyl-2-[methyl(methylsulfonyl)amino]pyrimid- in-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid of formula (I), as well as processes for their manufacture, pharmaceutical compositions containing them, and their uses ##STR00001##
![Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 1](http://www.wikipatents.com/drug-combinations-comprising-e-7-4-4-fluorophenyl-6-isopropyl-2-meth--ylsulfonylamino-pyrimidin-5-yl-3r5s--35-dihydroxyhept-6-enoic-acid-and-an-inhibitor-inducer-or-substrate-of-p450-isoenzyme-3a4/T/US6982157-1.jpg "Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 1")
![Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 2](http://www.wikipatents.com/drug-combinations-comprising-e-7-4-4-fluorophenyl-6-isopropyl-2-meth--ylsulfonylamino-pyrimidin-5-yl-3r5s--35-dihydroxyhept-6-enoic-acid-and-an-inhibitor-inducer-or-substrate-of-p450-isoenzyme-3a4/T/US6982157-2.jpg "Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 2")
![Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 3](http://www.wikipatents.com/drug-combinations-comprising-e-7-4-4-fluorophenyl-6-isopropyl-2-meth--ylsulfonylamino-pyrimidin-5-yl-3r5s--35-dihydroxyhept-6-enoic-acid-and-an-inhibitor-inducer-or-substrate-of-p450-isoenzyme-3a4/T/US6982157-3.jpg "Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 3")
![Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 4](http://www.wikipatents.com/drug-combinations-comprising-e-7-4-4-fluorophenyl-6-isopropyl-2-meth--ylsulfonylamino-pyrimidin-5-yl-3r5s--35-dihydroxyhept-6-enoic-acid-and-an-inhibitor-inducer-or-substrate-of-p450-isoenzyme-3a4/T/US6982157-4.jpg "Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 4")
![Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 5](http://www.wikipatents.com/drug-combinations-comprising-e-7-4-4-fluorophenyl-6-isopropyl-2-meth--ylsulfonylamino-pyrimidin-5-yl-3r5s--35-dihydroxyhept-6-enoic-acid-and-an-inhibitor-inducer-or-substrate-of-p450-isoenzyme-3a4/T/US6982157-5.jpg "Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 5")
![Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 6](http://www.wikipatents.com/drug-combinations-comprising-e-7-4-4-fluorophenyl-6-isopropyl-2-meth--ylsulfonylamino-pyrimidin-5-yl-3r5s--35-dihydroxyhept-6-enoic-acid-and-an-inhibitor-inducer-or-substrate-of-p450-isoenzyme-3a4/T/US6982157-6.jpg "Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[meth- ylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 - US Patent 6982157 - Page 6")
