EP1150679A1 - Use of cholesterol-lowering agent - Google Patents
Use of cholesterol-lowering agentInfo
- Publication number
- EP1150679A1 EP1150679A1 EP00901748A EP00901748A EP1150679A1 EP 1150679 A1 EP1150679 A1 EP 1150679A1 EP 00901748 A EP00901748 A EP 00901748A EP 00901748 A EP00901748 A EP 00901748A EP 1150679 A1 EP1150679 A1 EP 1150679A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- levels
- lowering
- per day
- pharmaceutically acceptable
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Definitions
- the present invention relates to the use of a cholesterol-lowering agent, and more particularly to the administration of a particular dose or dosage range of the HMG CoA reductase inhibitor, (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-
- the Agent [methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid and pharmaceutically acceptable salts thereof, hereinafter referred to as "the Agent” and illustrated (as the calcium salt) in formula I hereinafter.
- the invention further relates to the dosage range, start dose and dosage forms of the Agent.
- the Agent is disclosed in European Patent Application, Publication No. 0521471, and in Bioorganic and Medicinal Chemistry, (1997), 5(2), 437-444 as an inhibitor of 3-hydroxy-3- methylglutaryl CoA reductase (HMG-CoA reductase) which is a major rate-limiting enzyme in cholesterol biosynthesis.
- HMG-CoA reductase inhibitors are the most widely used prescription medication for the treatment of hypercholesterolaemia.
- a number of HMG-CoA reductase inhibitors are marketed, namely lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin and cerivastatin, and are collectively referred to as 'statins'.
- statin therapy less than optimal results may be achieved in patients, due to the level of efficacy and safety achieved at the recommended dosages of the currently marketed statins. Accordingly it is important to find dosages of alternative statins which beneficially alter lipid levels to a significantly greater extent than similar dosages of currently used statins and which have a similar or improved safety profile.
- the Agent lowers total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) by an unexpected degree, and without any significant adverse side effects.
- the Agent also modifies other lipoprotein levels (such as raising high density lipid cholesterol (HDL-C) levels, lowering triglyceride (TG) levels and lowering apolipoprotein B-100 (Apo-B) levels) to an unexpected and beneficial extent, without any significant adverse side effects.
- HDL-C high density lipid cholesterol
- TG lowering triglyceride
- Apo-B lowering apolipoprotein B-100
- ALT alanine aminotransferase
- one aspect of the present invention comprises a method of lowering LDL-C levels by 40% or more, and/or lowering total cholesterol levels by 30% or more, and/or lowering triglyceride levels by 10% or more, and/or lowering apolipoprotein B-100 levels by 30% or more, and/or raising HDL-C levels by 5% or more, in a patient in need thereof, by administration of 5 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of treatment of hypercholesterolemia in a patient in need thereof by administration of 5 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of lowering LDL-C levels by 40% or more in a patient in need thereof by administration of 5 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of lowering LDL-C levels by 45% or more in a patient in need thereof by administration of 10 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of lowering LDL-C levels by 50% or more in a patient in need thereof by administration of 10 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of lowering LDL-C levels by 55% or more in a patient in need thereof by administration of 20 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of lowering LDL-C levels by 60% or more in a patient in need thereof by administration of 40 to 80 mg per day of the Agent.
- a preferred feature of the present invention comprises a method of treatment as described above wherein the LDL-C level of the patient prior to treatment with the Agent, when measured after 12 hours of fasting (water permitted) is 4J mmol/litre or more.
- a further aspect of the present invention comprises a method of lowering total cholesterol levels by 30% or more in a patient in need thereof by administration of 10 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of lowering total cholesterol levels by 35% or more in a patient in need thereof by administration of 10 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of lowering total cholesterol levels by 40% or more in a patient in need thereof by administration of 40 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of treating a hypercholesterolemic patient to bring said patient within recommended NCEP guidelines (or other recognised guidelines) by administration of 5 to 80 mg per day of the Agent.
- Recommended NCEP guidelines refer to the National Cholesterol Education Program - Adult Treatment Panel (NCEP-ATP) II target LDL-C levels, which are incorporated herein by reference. A summary of these guidelines is given in JAMA, June 16, 1993-Vol 629, No. 23, pages 3015-3023, particularly Figue 1 , page 3018-3019.
- NCEP guidelines recommend that patients with clinically evident coronary heart disease (CHD), such as documented atherosclerosis, are titrated to LDL-C concentrations less than or equal to 100 mg/dl.
- CHD clinically evident coronary heart disease
- NCEP guidelines recommend aggressive management of lipids in such patients with a target LDL-C of 115 mg/dl. Where a patient has no clinically evident CHD, but has 2 or more risk factors for such a disease, NCEP guidelines recommend patients are titrated to LDL-C concentrations less than 130 mg/ml. Where a patient has no clinically evident CHD and one or no risk factors, the NCEP guideline target is less than 160 mg/dl.
- a further aspect of the present invention comprises a method of treating hypertriglyceridemia by administration of 5 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of raising high density lipid (HDL) levels in a patient in need thereof by administration of 5 to 80 mg per day of the Agent.
- HDL high density lipid
- a further aspect of the present invention comprises a method of raising or maintaining HDL levels whilst lowering LDL-C levels in a patient in need thereof by administration of 5 to 80 mg per day of the Agent.
- Preferred levels of lowering LDL-C levels, whilst maintaining or raising HDL levels include the percentage levels of reduction in LDL-C given in the above methods.
- a further aspect of the present invention comprises a method of lowering Apolipoprotein B levels in a patient in need thereof by administration of 5 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of treatment of mixed hyperlipidemia in a patient in need thereof by administration of 5 to 80 mg per day of the Agent.
- a further aspect of the present invention comprises a method of treatment of atherosclerosis in a patient in need thereof by administration of 5 to 80 mg per day of the Agent.
- 40 to 80 mg per day is referred to herein, other particular dosage ranges which are further independent aspects of the invention include (as appropriate) 10 to 80 mg per day, 10 to 60 mg per day, 10 to 40 mg per day, 5 to 40 mg per day, 5 to 20 mg per day, 10 to 20 mg per day, 20 to 60 mg per day, 20 to 40 mg per day and 40 to 60 mg per day. Accordingly, for the avoidance of doubt, particular independent aspects of the present invention comprise the following:-
- B-100 levels by 25% or more by administration of 1 to 5 mg per day of the Agent; (2) a method of lowering LDL-C levels by 45% or more and lowering apolipoprotein B-100 levels by 35% or more by administration of 5 to 20 mg per day (particularly 5 to 10 mg per day) of the Agent; (3) a method of lowering LDL-C levels by 50% or more and lowering apolipoprotein
- B-100 levels by 40% or more by administration of 10 to 20 mg per day of the Agent; (4) a method of lowering LDL-C levels by 55% or more and lowering apolipoprotein B-100 levels by 45% or more by administration of 20 to 40 mg per day of the Agent; or
- Further aspects of the present invention comprise the following:-
- (6) a method of lowering LDL-C levels by 60% or more, raising HDL-C levels by 5% (more particularly 8%) or more and lowering triglyceride levels by 10% or more in a patient in need thereof by administration of 40 to 80 mg per day of the Agent.
- a particularly suitable starting dose of the Agent in the methods referred herein is 5 to 10 mg per day, especially 10 mg per day. After initiation and/or upon titration of the Agent, lipid levels may be analysed and the dosage adjusted accordingly.
- a further aspect of the invention is therefore a method as defined above when the Agent is administered at a starting dose of 5 or 10 mg per day, for example a method of lowering LDL-C levels in a patient in need thereof by 40% or more by administration of 5 or 10 mg per day of the Agent.
- a further aspect of the present invention comprises a dosing regime comprising administration of a starting dose of 5 or 10 mg per day of the Agent to a patient in need thereof, such as a patient with an LDL-C level of 160 mg/dl or greater with no chronic heart disease (CHD) or peripheral vascular disease (PVD) and 1 or no risk factors, a patient with an LDL-C level of greater than 130 mg/dl with no CHD or PVD and with 2 or more risk factors, or a patient with an LDL-C level of greater than 100 mg/dl with clinically evident CHD or PVD.
- a dosing regime comprising administration of a starting dose of 5 or 10 mg per day of the Agent to a patient in need thereof, such as a patient with an LDL-C level of 160 mg/dl or greater with no chronic heart disease (CHD) or peripheral vascular disease (PVD) and 1 or no risk factors, a patient with an LDL-C level of greater than 130 mg/dl with no CHD or PVD and
- Another particular group of patients who are beneficially treated by administration of a start dose of 5 or 10 mg per day of the Agent includes, for example, those patients whose LDL-C level is >4 mmol/liter and/or whose TC level is >5 mmol/litre and/or whose HDL-C level is ⁇ 1 mmol/litre and/or whose TG level is > 2mmol/litre.
- a starting dose of 5 or 10 mg per day of the Agent unexpectedly has a superior efficacy and a comparable or better safety profile compared to the starting doses of other statins, and is therefore particularly advantageous.
- the Agent will be administered to a patient in the form of a pharmaceutical composition.
- a further aspect of the invention is therefore a pharmaceutical composition which comprises 5 to 80 mg of the Agent together with a pharmaceutically acceptable excipient or diluent.
- Particular pharmaceutical compositions which themselves are further independent aspects of the invention comprise, for example, 5 mg, 10 mg, 20 mg, 40 mg and 80 mg of the Agent together with a pharmaceutically acceptable excipient or diluent.
- the pharmaceutical compositions will be in the form of a conventional dosage unit form, for example, tablets or capsules.
- a further aspect of the invention comprises, a tablet or capsule containing the Agent in the amounts given above.
- the compositions of the invention may be obtained by conventional procedures using conventional pharmaceutical excipients, well known in the art.
- the Agent is administered as a single dose once daily.
- a further aspect of the invention comprises the use of the Agent in the amount specified for the manufacture of a medicament for use in said methods of treatment.
- the Agent is 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.
- a dose of (or a pharmaceutical composition comprising) 5 mg, 10 mg, 20 mg, 40 mg or 80 mg of the Agent is referred to, this includes a dose (or pharmaceutical composition comprising) of 5.2 mg, 10.4 mg, 20.8 mg, 41.6 mg and 83.2 mg respectively of the calcium salt of formula 1.
- Such doses (or compositions) are calculated to provide the equivalent of 5 mg, 10 mg, 20 mg, 40 mg and 80 mg respectively of the free acid form when dosed.
- Capsules containing 1, 2.5 or 10 mg of the Agent may be obtained similarly using more or less lactose as appropriate to maintain a total fill weight of 105 mg.
- Preferred such formulations are those in which the Agent is 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.
- the primary objective of this trial was to estimate the dose-response relationship between the dose of ZD4522 and the percentage reduction of LDL-C from the baseline value with respect to placebo. Secondary objectives
- atorvastatin doses (10 or 80 mg ), supplied open labelled, or to placebo or 1 of 6 ZD4522 doses ( supplied blinded). Analysis of the blinded portion of the trial addressed the primary objective.
- the open atorvastatin groups were included to obtain additional data on the starting and high doses, of a proven cholesterol-lowering agent in this patient population.
- the primary endpoint on which the sample size is based is on percentage reduction from baseline in LDL-C (LDL cholesterol) values.
- a sample size of 9 in each group will have 90%) power to detect a difference in means of 25% between 2 groups, assuming that the common standard deviation is 15%, using a 2 group t-test with a 0.05 two-sided significance level. This has been increased to 12 subjects per group to adjust for multiple comparisons of groups against placebo while preserving a power of at least 90% (based on simulations).
- This sample size also leads to an estimate of the dose-response curve for percentage decline in LDL-C with a width of the confidence band less than 10% for most of the dose range.
- HMG-CoA reductase inhibitors (2) History of serious or hypersensitivity reactions to other HMG-CoA reductase inhibitors. (3) Subjects with active arterial disease such as unstable angina, myocardial infarction, transient ischaemic attack (TIA), cerebro vascular accident (CVA) or coronary artery bypass graft (CABG) within 6 months or angioplasty within 3 months of study entry.
- active arterial disease such as unstable angina, myocardial infarction, transient ischaemic attack (TIA), cerebro vascular accident (CVA) or coronary artery bypass graft (CABG)
- Uncontrolled hypertension diastolic blood pressure ⁇ 95 mm Hg. Subjects who are taking thiazide diuretics and beta blockers will not be excluded provided they are maintained at a stable dose from 3 months before starting the study and throughout the study. (6) Diabetes mellitus and/or other metabolic endocrine disease known to be associated with alterations in plasma lipid levels (uncontrolled hypothyroidism defined as a TSH>1.5 times the ULN at week -6, subjects with nephrotic syndrome).
- HRT hormone replacement therapy
- the subjects were requested to take the study drug once daily, not less than 3 hours after the evening meal.
- Visits 1, 2, 3, 4, 6, 7, 8, 9 and 10 the trial subjects reported to the clinic after fasting for twelve hours (water permitted) and blood was drawn to determine fasting lipids.
- Subjects provided a urine sample, and blood samples for haematology and clinical biochemistry evaluation. Where lipid and clinical biochemistry measurements fell at the same visit, only one sample was taken.
- Visits 4, 6, 7 and 8 pharmacokinetic samples were collected. Weight, blood pressure and heart rate were measured and recorded at all visits.
- an ECG was performed.
- the analytical laboratory used is certified for standardisation of lipid analysis as specified by the Standardisation programme of the Centres for Disease Control and Prevention and the National Heart, Lung and Blood Institute.
- Full blood count was performed and included the following; erythrocyte count, haemoglobin, haematocrit, leucocyte cell count, platelets, red cell distribution width, percentage differential leukocyte count (including percentage large unstained cells), mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration.
- a clotting screen was performed at Visits 1 and 10 only.
- a positive value indicates a mean % increase of the lipid parameter level and a negative value indicates a mean % reduction of the lipid parameter level
- Study Arm Lipid Ratios (mean value at week 6) non HDL-C/HDL-C TC/HDL-C LDL-C/HDL-C
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9902590 | 1999-02-06 | ||
GBGB9902590.0A GB9902590D0 (en) | 1999-02-06 | 1999-02-06 | Use of cholesterol-lowering agent |
GBGB9921062.7A GB9921062D0 (en) | 1999-09-08 | 1999-09-08 | Use of cholestrol-lowering agent |
GB9921062 | 1999-09-08 | ||
PCT/GB2000/000285 WO2000045819A1 (en) | 1999-02-06 | 2000-02-01 | Use of cholesterol-lowering agent |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1150679A1 true EP1150679A1 (en) | 2001-11-07 |
Family
ID=26315084
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP00901748A Withdrawn EP1150679A1 (en) | 1999-02-06 | 2000-02-01 | Use of cholesterol-lowering agent |
Country Status (22)
Country | Link |
---|---|
EP (1) | EP1150679A1 (pt) |
JP (2) | JP2002536333A (pt) |
KR (1) | KR100699287B1 (pt) |
CN (1) | CN1347320A (pt) |
AR (1) | AR022462A1 (pt) |
AU (1) | AU769897B2 (pt) |
BR (1) | BR0007991A (pt) |
CA (1) | CA2358641A1 (pt) |
CZ (1) | CZ20012631A3 (pt) |
EE (1) | EE04659B1 (pt) |
HK (1) | HK1040924A1 (pt) |
HU (1) | HUP0105019A3 (pt) |
ID (1) | ID30131A (pt) |
IL (1) | IL144662A0 (pt) |
IS (1) | IS5996A (pt) |
MY (1) | MY136382A (pt) |
NO (1) | NO319827B1 (pt) |
NZ (1) | NZ512681A (pt) |
PL (1) | PL349137A1 (pt) |
SK (1) | SK11112001A3 (pt) |
TR (1) | TR200102236T2 (pt) |
WO (1) | WO2000045819A1 (pt) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0001621D0 (en) * | 2000-01-26 | 2000-03-15 | Astrazeneca Ab | Pharmaceutical compositions |
GB0003305D0 (en) | 2000-02-15 | 2000-04-05 | Zeneca Ltd | Pyrimidine derivatives |
SE0103509D0 (sv) * | 2001-10-19 | 2001-10-19 | Astrazeneca Ab | Rosuvastatin in pre demented states |
GB0322552D0 (en) | 2003-09-26 | 2003-10-29 | Astrazeneca Uk Ltd | Therapeutic treatment |
WO2007142581A1 (en) * | 2006-06-07 | 2007-12-13 | Astrazeneca Ab | Combination product for the treatment or prevention of dyslipidaemia |
US8436028B2 (en) | 2007-06-20 | 2013-05-07 | Merck Sharp & Dohme Corp | CETP inhibitors derived from benzoxazole arylamides |
US8293721B2 (en) | 2007-06-20 | 2012-10-23 | Merck Sharpe & Dohme Corp. | CETP inhibitors derived from benzoxazole arylamides |
WO2008156715A1 (en) | 2007-06-20 | 2008-12-24 | Merck & Co., Inc. | Cetp inhibitors derived from benzoxazole arylamides |
EP2216095A1 (en) * | 2009-01-27 | 2010-08-11 | Koninklijke Philips Electronics N.V. | Microfluidic device for full blood count |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5260446A (en) * | 1989-12-22 | 1993-11-09 | Basf Aktiengesellschaft | Aminothiazoles |
JP2648897B2 (ja) * | 1991-07-01 | 1997-09-03 | 塩野義製薬株式会社 | ピリミジン誘導体 |
-
2000
- 2000-01-31 AR ARP000100408A patent/AR022462A1/es unknown
- 2000-02-01 WO PCT/GB2000/000285 patent/WO2000045819A1/en active IP Right Grant
- 2000-02-01 ID IDW00200101666A patent/ID30131A/id unknown
- 2000-02-01 KR KR1020017009822A patent/KR100699287B1/ko active IP Right Review Request
- 2000-02-01 JP JP2000596939A patent/JP2002536333A/ja not_active Withdrawn
- 2000-02-01 EP EP00901748A patent/EP1150679A1/en not_active Withdrawn
- 2000-02-01 CA CA002358641A patent/CA2358641A1/en not_active Abandoned
- 2000-02-01 AU AU23051/00A patent/AU769897B2/en not_active Revoked
- 2000-02-01 CN CN00803519A patent/CN1347320A/zh active Pending
- 2000-02-01 IL IL14466200A patent/IL144662A0/xx unknown
- 2000-02-01 BR BR0007991-0A patent/BR0007991A/pt not_active Application Discontinuation
- 2000-02-01 EE EEP200100404A patent/EE04659B1/xx not_active IP Right Cessation
- 2000-02-01 HU HU0105019A patent/HUP0105019A3/hu unknown
- 2000-02-01 TR TR2001/02236T patent/TR200102236T2/xx unknown
- 2000-02-01 NZ NZ512681A patent/NZ512681A/en not_active IP Right Cessation
- 2000-02-01 CZ CZ20012631A patent/CZ20012631A3/cs unknown
- 2000-02-01 SK SK1111-2001A patent/SK11112001A3/sk not_active Application Discontinuation
- 2000-02-01 PL PL00349137A patent/PL349137A1/xx not_active Application Discontinuation
- 2000-02-04 MY MYPI20000415A patent/MY136382A/en unknown
-
2001
- 2001-07-10 IS IS5996A patent/IS5996A/is unknown
- 2001-08-03 NO NO20013810A patent/NO319827B1/no active IP Right Review Request
-
2002
- 2002-04-10 HK HK02102713.0A patent/HK1040924A1/zh unknown
-
2011
- 2011-02-22 JP JP2011035406A patent/JP2011137023A/ja active Pending
Non-Patent Citations (1)
Title |
---|
See references of WO0045819A1 * |
Also Published As
Publication number | Publication date |
---|---|
BR0007991A (pt) | 2001-11-06 |
HUP0105019A3 (en) | 2003-02-28 |
NO319827B1 (no) | 2005-09-19 |
CZ20012631A3 (cs) | 2001-10-17 |
WO2000045819A1 (en) | 2000-08-10 |
HK1040924A1 (zh) | 2002-06-28 |
PL349137A1 (en) | 2002-07-01 |
JP2011137023A (ja) | 2011-07-14 |
AU769897B2 (en) | 2004-02-05 |
NO20013810L (no) | 2001-10-03 |
EE04659B1 (et) | 2006-08-15 |
NZ512681A (en) | 2003-12-19 |
TR200102236T2 (tr) | 2001-12-21 |
ID30131A (id) | 2001-11-08 |
AU2305100A (en) | 2000-08-25 |
AR022462A1 (es) | 2002-09-04 |
CN1347320A (zh) | 2002-05-01 |
IS5996A (is) | 2001-07-10 |
MY136382A (en) | 2008-09-30 |
CA2358641A1 (en) | 2000-08-10 |
IL144662A0 (en) | 2002-05-23 |
SK11112001A3 (sk) | 2002-02-05 |
KR100699287B1 (ko) | 2007-03-26 |
HUP0105019A2 (hu) | 2002-05-29 |
JP2002536333A (ja) | 2002-10-29 |
KR20010089631A (ko) | 2001-10-06 |
NO20013810D0 (no) | 2001-08-03 |
EE200100404A (et) | 2002-10-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100815042B1 (ko) | 이형접합성 가족성 고콜레스테롤혈증 치료에 있어서로수바스타틴(zd-4522)의 용도 | |
Miller et al. | Clinical pharmacokinetics of fibric acid derivatives (fibrates) | |
JP2011137023A (ja) | コレステロール低下薬の使用 | |
EP0671171A1 (en) | Use of HMG COA reductase inhibitor for the manufacture of a medicament for proventing or reducing risks of onset of cardiovascular events | |
AU2002214165A1 (en) | Use of rosuvastatin (ZD-4522) in the treatment of heterozygous familial hypercholesterolemia | |
US20140121229A1 (en) | Combination comprising s-[2-([[1-(2-ethylbutyl)cyclohexyl] carbonyl]amino)phenyl] 2-methylpropanethioate and an hmg coa reductase inhibitor | |
JP2007277267A (ja) | (e)−7−[4−(4−フルオロフェニル)−6−イソプロピル−2−[メチル(メチルスルホニル)アミノ]ピリミジン−5−イル](3r,5s)−3,5−ジヒドロキシヘプツ−6−エン酸と、p450アイソザイム3a4の阻害剤、誘導剤又は基質を含んでなる薬物の組み合わせ | |
JP2006520810A (ja) | S−[2−([[1−(2−エチルブチル)シクロヘキシル]カルボニル]アミノ)フェニル]2−メチルプロパンチオエートの経口吸収性を増加させる方法 | |
EP1272219B1 (en) | New combination of a betablocker and a cholesterol-lowering agent | |
Whitfield et al. | Effect of food on the pharmacodynamics and pharmacokinetics of atorvastatin, an inhibitor of HMG-CoA reductase | |
CN100566719C (zh) | 用于治疗尤其是在糖尿病患者中的肾的功能障碍、疾病或者病症的药物组合物 | |
TWI302457B (en) | A pharmaceutical composition for improving blood lipid or reducing blood homocysteine | |
AU2016222441A1 (en) | Compound preparation of lercanidipine and atorvastatin | |
MXPA01007294A (es) | Uso de un agente que reduce colesterol | |
WO2007142581A1 (en) | Combination product for the treatment or prevention of dyslipidaemia |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20010906 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE |
|
AX | Request for extension of the european patent |
Free format text: AL PAYMENT 20010906;LT PAYMENT 20010906;LV PAYMENT 20010906;MK PAYMENT 20010906;RO PAYMENT 20010906;SI PAYMENT 20010906 |
|
17Q | First examination report despatched |
Effective date: 20031028 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20060506 |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1040924 Country of ref document: HK |