5 10 20 Crestor 5, 10, 20mg Film-Coated Tablets CRESTOR (rosuvastatin calcium) 3-hydroxy-3-methylglutaryl- coenzyme A(HMG-CoA 酶 HMG-CoA mevalonate Rosuvastatin calcium bis[(e)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl) amino] pyrimidin-5-yl](3r,5s)-3,5-dihydroxyhept-6-enoic acid] calcium salt Rosuvastatin calcium (C 22 H 27 FN 3 O 6 S) 2 Ca 1001.14 F OH OH O N N N SO 2 Me O Ca 2+ 2 Rosuvastatin calcium Rosuvastatin ph 7.0 - (octanol/water 0.13 5 10 20 rosuvastatin (tribasic calcium phosphatecrospovidone (hypromellose (triacetin (TG (lipoprotein complex (VLDL (IDL (LDL B-100 (ApoB-100 (HDL 酶 (lipase ApoB/E 1
(LDL-C (HDL-C) (remnants) (CHD Rosuvastatin HMG-CoA 酶 酶 3-hydroxy-3- methylglutaryl coenzyme A mevalonate mevalonate rosuvastatin rosuvastatin (FH rosuvastatin B ( Rosuvastatin (isolated hypertriglyceridemia rosuvastatin (VLDL-C) B rosuvastatin 3-5 rosuvastatin (C max (AUC) rosuvastatin Rosuvastatin 20% C max AUC rosuvastatin 20% Rosuvastatin rosuvastatin Rosuvastatin 134 88% rosuvastatin 2
Rosuvastatin 10% N-desmethyl rosuvastatin P450 2C9 N-desmethyl rosuvastatin HMG-CoA 酶 rosuvastatin HMG-CoA 酶 90% rosuvastatin rosuvastatin (90%Rosuvastatin 19 28% 72% ( (AUC C max ) 2 ( : / : rosuvastatin ( 65 rosuvastatin 18 10-17 (FH (9 9 ) rosuvastatin rosuvastatin C max AUC rosuvastatin 20 mg 14 ( 30 ml/min/1.73m 2 rosuvastatin ( 30 ml/min) rosuvastatin ( CL cr 80 ml/min/1.73m 2 ) 3 ( : rosuvastatin 50% rosuvastatin Childs-Pugh A C max AUC 60% 5% Childs-Pugh B C max AUC 100% 21%( : P450 3A4 rosuvastatin P450 3A4 P450 3A4 (ketoconazole erythromycin itraconazole Ketoconazole Ketoconazole(200 mg 7 rosuvastatin(80 mg rosuvastatin Erythromycin Erythromycin(500 mg 7 rosuvastatin(80 mg rosuvastatin AUC 20% C max 31% 3
Itraconazole Itraconazole(200 mg 5 rosuvastatin 10 mg 80 mg rosuvastatin AUC 39% 28% Fluconazole Fluconazole(200 mg 11 rosuvastatin 80 mg rosuvastatin AUC 14% Cyclosporine Cyclosporine rosuvastatin cyclosporine rosuvastatin C max AUC 11 7 ( : / Warfarin: Warfarin (25 mgrosuvastatin (40 mg) warfarin (INR) ( : Digoxin Digoxin (0.5 mgrosuvastatin (40 mg) digoxin Fenofibrate Fenofibrate (67 mg rosuvastatin (10 mg rosuvastatin fenofibrate ( : / Gemfibrozil Gemfibrozil(600 mg 7 rosuvastatin (80 mg rosuvastatin AUC C max 90% 120% ( : : / Antacid ( rosuvastatin(40 mg rosuvastatin 54% rosuvastatin 2 rosuvastatin ( : (ethinyl estradiol norgestrelrosuvastatin ethinyl estradiol norgestrel 26% 34% ( (Fredrickson IIa IIb ) CRESTOR B CRESTOR 4
CRESTOR 6 B ( 1 1. CRESTOR ( 6 ) B 13-5 -7-7 -3-3 3 5 17-33 -45-44 -38-35 13 10 17-36 -52-48 -42-10 14 20 17-40 -55-51 -46-23 8 40 18-46 -63-60 -54-28 10 2,240 IIa IIb CRESTOR atorvastatin simvastatin pravastatin HMG-CoA 酶 CRESTOR atorvastatin simvastatin pravastatin 6 ( 1 2 1. 6 CRESTOR Atorvastatin Simvastatin Pravastatin IIa/IIb 25 50 75 10 90 189 mg/dl 2. 6 (LS means ) ( 156-167 ) 10 mg 20 mg 40 mg 80 mg CRESTOR -46* -52-55 -- Atorvastatin -37-43 -48-51 Pravastatin -20-24 -30 -- 5
Simvastatin -28-35 -39-46 *CRESTOR 10 mg atorvastatin 10 mg pravastatin 10 mg 20 mg 40 mg simvastatin 10 mg 20 mg 40 mg (p 0.002 CRESTOR 20 mg atorvastatin 20 mg 40 mg pravastatin 20 mg 40 mg simvastatin 20 mg 40 mg 80 mg (p 0.002 CRESTOR 40 mg atorvastatin 40 mg pravastatin 40 mg simvastatin 40 mg 80 mg (p 0.002 1.00 ( 291 CRESTOR 20 mg atorvastatin 20 mg 6 ( 3 3. CRESTOR (n=435) LS Means * (95% CI) Atorvastatin (n=187) LS Means (95% CI) 6 20 mg -47% (-49%, -46%) -38% (-40%, -36%) 12 40 mg -55% (-57%, -54%) -47% (-49%, -45%) 18 80 mg NA -52% (-54%, -50%) *LS Means (Fredrickson IIb IV ) 273-817 mg/dl CRESTOR (5-40 mg 6 ( 4 4. CRESTOR 6 ( CRESTOR N=26 5 mg N=25 CRESTOR 10 mg N=23 CRESTOR 20 mg N=27 CRESTOR 40 mg N=25 1 (-40, 72) -21 (-58, 38) -37 (-65, 5) -37 (-72, 11) -43 (-80, -7) 2 (-13, 19) -29 (-43, -8) -49 (-59, -20) -43 (-74, -12) -51 (-62, -6) 2 (-36, 53) -25 (-62, 49) -48 (-72, 14) -49 (-83, 20) -56 (-83, 10) 1 (-13, 17) -24 (-40, -4) -40 (-51, -14) -34 (-61, -11) -40 (-51, -4) 5 (-30, 52) -28 (-71, 2) -45 (-59, 7) -31 (-66, 34) -43 (-61, -3) -3 (-25, 18) 3 (-38, 33) 8 (-8, 24) 22 (-5, 50) 17 (-14, 63) 6
6 40 (n=40 8-63 CRESTOR 20-40 mg 22% 20 mg 40 mg 6% 27 15% 30%( 28% 13 15% 3 5 3 15% CRESTOR 1. ( (Fredrickson IIa IIb (LDL-C B(Apo B) (HDL-C 2. (Fredrickson IV 3. ( [LDL apheresis]) B(Apo B (NCEP-ATP III (TLC) 5 CHD a 5. (NCEP) CHD 100 mg/dl 100 mg/dl 130 mg/dl (10 20%) 2 130 mg/dl (10 20%) c 0-1 160 mg/dl 130 mg/dl 160 mg/dl (100-129 mg/dl ) b 10 10%-20% 130 mg/dl 10 10% 160 mg/dl 190 mg/dl (160-189 mg/dl ) 7
a CHD b 100 mg/dl nicotinic acid fibrate c 0-1 10 10% 0-1 10 200 mg/dl ( 30 mg/dl 130 mg/dl ( NCEP 20 5 CRESTOR ( 400 mg/dl( 4.5 mmol/l (0.20 [ ] ) 400 mg/dl ( 4.5 mmol/l) CRESTOR Fredrickson I III V CRESTOR Rosuvastatin ( : ( ) HMG-CoA 酶 HMG-CoA 酶 ROSUVASTATIN HMG-CoA 酶 rosuvastatin 5 10 20 40 mg ( [ULN] 3 0.4 0 0 0.1% 8
rosuvastatin 12 ( rosuvastatin ALT AST 3 rosuvastatin Rosuvastatin / ( : rosuvastatin ( / Rosuvastatin rosuvastatin ( 0.2-0.4% rosuvastatin 40 mg 酶 (creatine phosphokinase CK ( 10 0.1% rosuvastatin 40 mg 酶 (CK 10 rosuvastatin (5-40 mg / HMG-CoA 酶 ( rosuvastatin) ( HMG-CoA 酶 rosuvastatin (40 mg HMG-CoA 酶 ( 65 2. 酶 (CK rosuvastatin 3. Rosuvastatin cyclosporine ( CRESTOR fibrate niacin rosuvastatin gemfibrozil ( : 4. rosuvastatin rosuvastatin ( : 5. ( rosuvastatin 9
rosuvastatin ( ( 30 ml/min/1.73 m 2 rosuvastatin 20 mg rosuvastatin 3 ( / ( [Asian Indian] 2 rosuvastatin ( / rosuvastatin rosuvastatin 2 ( rosuvastatin rosuvastatin ( 80 mg) rosuvastatin statin rosuvastatin 40 mg Cyclosporine rosuvastatin 10 mg cyclosporine rosuvastatin C max AUC 11 7 cyclosporine rosuvastatin ( / Warfarin warfarin rosuvastatin 酶 (INR 4 2-3 coumarin rosuvastatin rosuvastatin INR INR coumarin INR rosuvastatin rosuvastatin INR Gemfibrozil gemfibrozil rosuvastatin (600 mg rosuvastatin C max AUC 2.2 1.9 ( rosuvastatin (cortisol) (adrenal reserve HMG-CoA 酶 ( ketoconazole spironolactone cimetidine 10
HMG-CoA 酶 rosuvastatin HMG-CoA 酶 30 ( [Wallerian degeneration] rosuvastatin 90 mg( AUC 40 mg 100 24 (choroid plexus) rosuvastatin 6 mg( AUC 40 mg 20 ) 52 rosuvastatin 30 mg( AUC 40 mg 60 ) 12 rosuvastatin 90 mg( AUC 40 mg 100 4 30 mg ( AUC 40 mg 60 ) 104 rosuvastatin 2 20 60 80 mg 80 mg ( AUC 40 mg 20 107 rosuvastatin 10 60 200 mg 200 mg ( AUC 40 mg 20 / Ames rosuvastatin Rosuvastatin rosuvastatin 5 15 50 mg 9 atorvastatin 2 7 rosuvastatin rosuvastatin 50 mg ( AUC 40 mg 10 ) rosuvastatin 30 mg (spermatidic giant cells) rosuvastatin 30 mg AUC 40 mg 20 10 HMG-CoA 酶 X rosuvastatin Rosuvastatin rosuvastatin Rosuvastatin 16 rosuvastatin 25 mg rosuvastatin 3% 20% 18 rosuvastatin 1 mg ( 25%) 11
7 rosuvastatin 5 15 50 mg ( AUC 40 mg 10 ) ( ) 7 21 ( ) rosuvastatin 2 10 50 mg 50 ( 40 mg 12 6 18 ( rosuvastatin 0.3 1 3 mg ( 40 mg ) rosuvastatin 25 mg rosuvastatin 3 mg ( AUC 40 mg ) rosuvastatin rosuvastatin 3 rosuvastatin CRESTOR 8 8 rosuvastatin 10,275 3,159 (31%65 698 (6.8%75 65 65 ( / Rosuvastatin 10,275 3.7% rosuvastatin rosuvastatin rosuvastatin 2% 6 12 rosuvastatin 3% 5% 6. Rosuvastatin N=744 N=382 12
9.0 7.6 5.5 5.0 3.4 2.9 3.4 3.1 3.4 3.1 2.8 1.3 2.7 2.6 2.6 2.4 2.3 1.8 2.3 1.6 2.2 2.1 2.0 1.8 rosuvastatin 10,275 1% 2% rosuvastatin rosuvastatin ( 80 mg) rosuvastatin statin rosuvastatin 40 mg ( 酶 肽 酶 (glutamyl transpeptidase 酶 rosuvastatin 1% ( CRESTOR 13
rosuvastatin CRESTOR CRESTOR ( (Fredrickson IIa IIb ) CRESTOR 5-20 mg CRESTOR 10 mg 5 mg cyclosporine ( ( 190 mg/dl 20 mg CRESTOR / 2-4 statin statin CRESTOR CRESTOR CRESTOR 20 mg CRESTOR ( [LDL apheresis] 5 mg CRESTOR 5 10 mg rosuvastatin ( : / : Cyclosporine cyclosporine CRESTOR 5 mg ( : / CRESTOR gemfibrozil CRESTOR 10 mg ( : / : 14
(CL cr 30 ml/min/1.73 m 2 CRESTOR 5 mg 10 mg ( 圓 形, 黃 色 (5 毫 克 ); 圓 形, 粉 紅 色 (10 毫 克 及 20 毫 克 ) 30 2006 12 5mg IPR Pharmaceuticals Inc. San Isidro Industrial Park, Canovanas, Puerto Rico 00729 10mg, 20mg IPR Pharmaceuticals Inc. South Main Street, Sabana Gardens, Industrial Park, Carolina, Puerto Rico 00984 AstraZeneca UK Limited Silk Road Business Park Macclesfield, Cheshire, United Kingdom, SK10 2NA 207 21 23782390 15