Wikipedia

Rosuvastatin

Rosuvastatin,sold under the brand nameCrestoramong others, is astatinmedication, used to preventcardiovascular diseasein those at high risk and treatabnormal lipids.[6]It is recommended to be used together with dietary changes, exercise, and weight loss.[6]It is takenorally(by mouth).[6]

Rosuvastatin
Clinical data
Pronunciation/roʊˈsuːvəstætɪn/roh-SOO-və-stat-in
Trade namesCrestor, others
Other namesRosuvastatin calcium (USANUS)
AHFS/Drugs.comMonograph
MedlinePlusa603033
License data
Pregnancy
category
Routes of
administration		Oral(by mouth)
ATC code
Legal status
Legal status
Pharmacokineticdata
Bioavailability20%[5][6]
Protein binding88%[5][6]
MetabolismLiver:CYP2C9(major) andCYP2C19-mediated; ~10% metabolized[5][6]
MetabolitesN-desmethyl rosuvastatin (major; 1/6–1/9 of rosuvastatin activity)[4]
Eliminationhalf-life19 hours[5][6]
ExcretionFeces(90%)[5][6]
Identifiers
  • (3R,5S,6E)-7-[4-(4-Fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid
CAS Number
PubChemCID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard(EPA)
ECHA InfoCard100.216.011Edit this at Wikidata
Chemical and physical data
FormulaC22H28FN3O6S
Molar mass481.54g·mol−1
3D model (JSmol)
  • OC(=O)C[C@H](O)C[C@H](O)\C=C\c1c(C(C)C)nc(N(C)S(=O)(=O)C)nc1c2ccc(F)cc2
  • InChI=1S/C22H28FN3O6S/c1-13(2)20-18(10-9-16(27)11-17(28)12-19(29)30)21(14-5-7-15(23)8-6-14)25-22(24-20)26(3)33(4,31)32/h5-10,13,16-17,27-28H,11-12H2,1-4H3,(H,29,30)/b10-9+/t16-,17-/m1/s1☒N
  • Key:BPRHUIZQVSMCRT-VEUZHWNKSA-N☒N
☒NcheckY(what is this?)(verify)

Common side effects include abdominal pain, nausea, headaches, andmuscle pains.[6]Serious side effects may includerhabdomyolysis,liver problems, anddiabetes.[6]Use duringpregnancymay harm the baby.[6]Like all statins, rosuvastatin works by inhibitingHMG-CoA reductase,anenzymefound in theliverthat plays a role in producingcholesterol.[6]

Rosuvastatin was patented in 1991, and approved for medical use in the United States in 2003.[6][7]It is available as ageneric medication.[6]In 2022, it was the thirteenth most commonly prescribed medication in the United States, with more than 37million prescriptions.[8][9]In Australia, it was one of the top 10 most prescribed medications between 2017 and 2023.[10]

Medical uses

edit
Rosuvastatin (marketed as Crestor) 10 mg tablets

The primary use of rosuvastatin is for prevention of cardiovascular disease in those at high risk and the treatment ofabnormal lipids.[6]

Effects on cholesterol levels

edit

The effects of rosuvastatin onlow-density lipoprotein(LDL) cholesterol are dose-related. Higher doses were more efficacious in improving the lipid profile of patients with hypercholesterolemia than milligram-equivalent doses ofatorvastatinand milligram-equivalent or higher doses ofsimvastatinandpravastatin.[11]

Meta-analysis showed that rosuvastatin is able to modestly increase levels ofhigh-density lipoprotein(HDL) cholesterol as well, as with other statins.[12]A 2014 Cochrane review determined there was good evidence for rosuvastatin lowering non-HDL levels linearly with dose.[13]

Side effects and contraindications

edit

Side effects are uncommon:[14]

The following rare side effects are more serious. Like all statins, rosuvastatin can possibly causemyopathy,rhabdomyolysis:[14][4]

Allergic reactions can develop:[4]

Rosuvastatin has multiplecontraindications,including hypersensitivity to rosuvastatin or any component of the formulation, active liver disease, elevation of serumtransaminases,pregnancy, or breastfeeding.[4]Rosuvastatin is not prescribed nor used while pregnant, as it can cause serious harm to the fetus.[4]In the case of breastfeeding, it is unknown whether rosuvastatin is passed through breastmilk.[4][15]

The risk of myopathy may be increased in Asian Americans: "Because Asians appear to process the drug differently, half the standard dose can have the same cholesterol-lowering benefit in those patients, though a full dose could increase the risk of side-effects, a study by the drug's manufacturer,AstraZeneca,indicated. "[16][17][18]Therefore, the lowest dose is recommended in Asians.[19]

Myopathy

edit

As with all statins, there is a concern ofrhabdomyolysis,a severe undesired side effect. The U.S.Food and Drug Administration(FDA) has indicated that "it does not appear that the risk [of rhabdomyolysis] is greater with Crestor than with other marketed statins", but has mandated that a warning about this side-effect, as well as a kidney toxicity warning, be added to the product label.[20][21]

Diabetes mellitus

edit

Statinsincrease the risk ofdiabetes,[22]consistent with FDA's review, which reported a 27% increase in investigator-reported diabetes mellitus in rosuvastatin-treated people.[23]

Drug interactions

edit

The following drugs can have negative interactions with rosuvastatin and should be discussed with the prescribing doctor:[14][4]

Grapefruit juice negatively interacts with several specific drugs in the statin class, but it has little or no effect on rosuvastatin.[25]

Structure

edit

Rosuvastatin has structural similarities with most otherstatins,e.g.,atorvastatin,cerivastatinandpitavastatin,but unlike other statins, rosuvastatin containssulfur(insulfonylfunctional group). Crestor is acalciumsalt of rosuvastatin, i.e. rosuvastatin calcium,[20]in which calcium replaces the hydrogen in thecarboxylic acidgroup on the right of the skeletal formula at the top right of this page.[citation needed]

Mechanism of action

edit
Further information:Statin

Rosuvastatin is acompetitive inhibitorof the enzymeHMG-CoA reductase,having a mechanism of action similar to that of other statins.[26]

Putative beneficial effects of rosuvastatin therapy on chronicheart failuremay be negated by increases in collagen turnover markers as well as a reduction in plasmacoenzyme Q10levels in patients with chronic heart failure.[27]

Pharmacodynamics

edit

The dose-related magnitude of rosuvastatin on blood lipids was determined in aCochranesystematic review in 2014. Over the dose range of 1 to 80 mg/day strong linear dose‐related effects were found; total cholesterol was reduced by 22.1% to 44.8%, LDL cholesterol by 31.2% to 61.2%, non-HDL cholesterol by 28.9% to 56.7% and triglycerides by 14.4% to 26.6%.[13]

Pharmacokinetics

edit

Absolutebioavailabilityof rosuvastatin is about 20% andCmaxis reached in 3 to 5 hours; administration with food did not affect theAUCaccording to the original sponsor submitted clinical study and as per product label.[4]However, a subsequent clinical study has shown a marked reduction in rosuvastatin exposure when administered with food.[28]It is 88%protein bound,mainly toalbumin.[6]Fraction absorbed of rosuvastatin is frequently misquoted in the literature as approximately 0.5 (50%)[29]due to a miscalculated hepatic extraction ratio in the original submission package subsequently corrected by the FDA reviewer.[30]

Rosuvastatin is metabolized mainly byCYP2C9and not extensively metabolized; approximately 10% is recovered asmetaboliteN-desmethyl rosuvastatin. It is excreted infeces(90%) primarily and theelimination half-lifeis approximately 19 hours.[4][6]

Both AUC and Cmaxare approximately 2-fold higher in Asian patients compared to Caucasian patients given the same dose of rosuvastatin.[4]

Society and culture

edit

Rosuvastatin is theinternational nonproprietary name (INN).[31]

Economics

edit

Because low- to moderate dose statins are strongly recommended by theUnited States Preventive Services Task Force(USPSTF) forprimary preventionof cardiovascular disease in adults aged 40–75 years who are at risk,[32]thePatient Protection and Affordable Care Act(PPACA) in the United States requires most health insurance plans to cover the costs of these drugs without charging the insured patient acopaymentorcoinsurance,even if he or she has not yet reached his or her annualdeductible.[33][34][35]Rosuvastatin 5 mg and 10 mg are examples of regimens meeting the USPSTF guideline;[32]however, insurers have discretion as to which low- and moderate-dose statin regimens to cover under this requirement,[36]and some only cover other statins.[37]

The drug was billed as a "super-statin" during its clinical development; the claim was that it offers high potency and improved cholesterol reduction compared to rivals in the class. The main competitors to rosuvastatin areatorvastatinandsimvastatin.However, people can also combineezetimibewith either simvastatin or atorvastatin and other agents on their own, for somewhat similar augmented response rates. As of 2006some published information for comparing rosuvastatin, atorvastatin, and ezetimibe/simvastatin results is available, but many of the relevant studies are still[when?]in progress.[26][needs update]

First launched in 2003, sales of rosuvastatin were $129million and $908million in 2003, and 2004, respectively, with a total patient treatment population of over 4million by the end of 2004.[citation needed] Annual cost to the UKNational Health Service(NHS) in 2018, for 5–40 mg rosuvastatin daily (of one person) was £24-40, compared to £10-20 for 20–80 mg simvastatin.[38]

In 2013, it was the fourth-highest selling drug in the United States, accounting for approximately $5.2billion in sales.[39]In 2021, it was the thirteenth most commonly prescribed medication in the United States, with more than 32million prescriptions.[40]

edit

Rosuvastatin is approved in the United States for the treatment of highLDL cholesterol(dyslipidemia), total cholesterol (hypercholesterolemia), and/ortriglycerides(hypertriglyceridemia).[41]In February 2010, rosuvastatin was approved by the FDA for the primary prevention of cardiovascular events.[42]

As of 2004,rosuvastatin had been approved in 154 countries and launched in 56. Approval in the United States by theFood and Drug Administration(FDA) came on 13 August 2003.[43][44]

Patent protection and generic versions

edit

The main patent which protected rosuvastatin (RE37,314, which expired in 2016) was challenged as being an improper reissue of an earlier patent. This challenge was rejected in 2010, and thus patent protection did continue until 2016.[45][46][47][48][49]

In April 2016, the FDA approved the firstgenericversion of rosuvastatin (from Watson Pharmaceuticals Inc).[50]In July 2016,Mylangained approval for its generic rosuvastatin calcium.[51]

Debate and criticisms

edit

In October 2003, several months after its introduction in Europe,Richard Horton,the editor of themedical journalThe Lancet,criticized the way Crestor had been introduced. "AstraZeneca's tactics in marketing its cholesterol-lowering drug, rosuvastatin, raise disturbing questions about how drugs enter clinical practice and what measures exist to protect patients from inadequately investigated medicines," according to his editorial.The Lancet'seditorial position is that the data for Crestor's superiority rely too much on extrapolation from the lipid profile data (surrogate end-points) and too little on hard clinical end-points, which are available for other statins that had been on the market longer. The manufacturer responded by stating that few drugs had been tested so successfully on so many patients. In correspondence published inThe Lancet,AstraZeneca's CEOTom McKillopcalled the editorial "flawed and incorrect" and slammed the journal for making "such an outrageous critique of a serious, well-studied medicine."[52]

In 2004, the consumer interest organizationPublic Citizenfiled aCitizen's Petitionwith the FDA, asking that Crestor be withdrawn from the US market. On 11 March 2005, the FDA issued a letter toSidney M. Wolfeof Public Citizen both denying the petition and providing an extensive detailed analysis of findings that demonstrated no basis for concerns about rosuvastatin compared with the other statins approved for marketing in the United States.[53]In 2015, Wolfe explained why he thought that "the drug should have been withdrawn and why it should not be used", due to the incidence of rhabdomyolysis, renal problems, and significant increase inglycated hemoglobin(HbA1C) and fastinginsulinlevels, and decreasedinsulin sensitivityin diabetic patients. Rosuvastatin indeed lowered cholesterol more than other statins, but Wolfe asked "what about actually improving health, preventing heart attacks and strokes?"[54]

References

edit
  1. ^"Rosuvastatin Use During Pregnancy".Drugs.com.27 September 2019.Archivedfrom the original on 30 November 2020.Retrieved14 March2020.
  2. ^"Crestor Product information".Health Canada.25 April 2012.Archivedfrom the original on 9 July 2021.Retrieved9 July2021.
  3. ^"Crestor 10mg film-coated tablets - Summary of Product Characteristics (SmPC)".(emc).29 September 2020.Archivedfrom the original on 9 July 2021.Retrieved9 July2021.
  4. ^abcdefghijklm"Crestor- rosuvastatin calcium tablet, film coated".DailyMed.9 November 2018.Archivedfrom the original on 25 September 2020.Retrieved14 March2020.
  5. ^abcdeAggarwal RK, Showkathali R (June 2013). "Rosuvastatin calcium in acute coronary syndromes".Expert Opinion on Pharmacotherapy.14(9): 1215–27.doi:10.1517/14656566.2013.789860.PMID23574635.S2CID20221457.
  6. ^abcdefghijklmnopq"Rosuvastatin Calcium Monograph for Professionals".Drugs.com.American Society of Health-System Pharmacists(AHFS).Archivedfrom the original on 24 December 2018.Retrieved24 December2018.
  7. ^Fischer J, Ganellin CR (2006).Analogue-based Drug Discovery.John Wiley & Sons. p. 473.ISBN9783527607495.Archivedfrom the original on 12 January 2023.Retrieved27 August2020.
  8. ^"The Top 300 of 2022".ClinCalc.Archivedfrom the original on 30 August 2024.Retrieved30 August2024.
  9. ^"Rosuvastatin Drug Usage Statistics, United States, 2013 - 2022".ClinCalc.Retrieved30 August2024.
  10. ^"Medicines in the health system".Australian Institute of Health and Welfare.2 July 2024.Retrieved30 September2024.
  11. ^Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. (2003). "Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial)".Am J Cardiol.92(2): 152–60.doi:10.1016/S0002-9149(03)00530-7.PMID12860216.
  12. ^McTaggart F (August 2008)."Effects of statins on high-density lipoproteins: a potential contribution to cardiovascular benefit".Cardiovasc Drugs Ther.22(4): 321–38.doi:10.1007/s10557-008-6113-z.PMC2493531.PMID18553127.
  13. ^abAdams SP, Sekhon SS, Wright JM (November 2014)."Rosuvastatin for lowering lipids".The Cochrane Database of Systematic Reviews.2014(11): CD010254.doi:10.1002/14651858.cd010254.pub2.PMC6463960.PMID25415541.
  14. ^abc"Rosuvastatin".MedlinePlus.U.S. National Library of Medicine. 15 June 2012.Archivedfrom the original on 6 November 2012.Retrieved1 December2012.
  15. ^"Rosuvastatin".LactMed.U.S. National Library of Medicine. Archived fromthe originalon 7 January 2016.Retrieved1 December2012.
  16. ^Alonso-Zaldivar R (3 March 2005)."FDA Advisory Targets Asian Patients".Los Angeles Times.Archivedfrom the original on 5 March 2016.Retrieved15 March2020.
  17. ^Wu HF, Hristeva N, Chang J, Liang X, Li R, Frassetto L, et al. (September 2017)."Rosuvastatin Pharmacokinetics in Asian and White Subjects Wild Type for Both OATP1B1 and BCRP Under Control and Inhibited Conditions".J Pharm Sci.106(9): 2751–2757.doi:10.1016/j.xphs.2017.03.027.PMC5675025.PMID28385543.
  18. ^Lee VW, Chau TS, Leung VP, Lee KK, Tomlinson B (December 2009)."Clinical efficacy of rosuvastatin in lipid management in Chinese patients in Hong Kong".Chin. Med. J.122(23): 2814–9.PMID20092783.Archivedfrom the original on 30 October 2019.Retrieved30 October2019.
  19. ^"FDA Updates Crestor Warning Information".WebMD.3 March 2005.Archivedfrom the original on 20 September 2020.Retrieved14 March2020.
  20. ^ab"FDA Alert (03/2005) - Rosuvastatin Calcium (marketed as Crestor) Information".U.S.Food and Drug Administration(FDA). 14 March 2005. Archived fromthe originalon 5 March 2005.Retrieved20 March2005.- This page is subject to change; the date reflects the last revision date.
  21. ^"Rosuvastatin Calcium (marketed as Crestor) Information".U.S.Food and Drug Administration(FDA).10 July 2015.Archivedfrom the original on 15 December 2019.Retrieved14 March2020.
  22. ^Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. (February 2010). "Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials".Lancet.375(9716): 735–42.doi:10.1016/S0140-6736(09)61965-6.PMID20167359.S2CID11544414.
  23. ^"FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs".U.S.Food and Drug Administration(FDA). 9 February 2019.Archivedfrom the original on 15 March 2020.Retrieved15 March2020.
  24. ^"Viberzi- eluxadoline tablet, film coated".DailyMed.19 June 2018.Archivedfrom the original on 28 September 2020.Retrieved14 March2020.
  25. ^Bailey DG, Dresser G, Arnold JM (March 2013)."Grapefruit-medication interactions: forbidden fruit or avoidable consequences?".CMAJ.185(4): 309–316.doi:10.1503/cmaj.120951.PMC3589309.PMID23184849.
  26. ^abNissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, et al. (April 2006). "Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial".JAMA.295(13): 1556–65.doi:10.1001/jama.295.13.jpc60002.PMID16533939.
  27. ^Ashton E, Windebank E, Skiba M, Reid C, Schneider H, Rosenfeldt F, et al. (February 2011). "Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistic insights from the UNIVERSE study".Int J Cardiol.146(3): 404–7.doi:10.1016/j.ijcard.2009.12.028.PMID20085851.
  28. ^Li Y, Jiang X, Lan K, Zhang R, Li X, Jiang Q (October 2007). "Pharmacokinetic properties of rosuvastatin after single-dose, oral administration in Chinese volunteers: a randomized, open-label, three-way crossover study".Clinical Therapeutics.29(10): 2194–203.doi:10.1016/j.clinthera.2007.10.005.PMID18042475.
  29. ^Bergman E, Lundahl A, Fridblom P, Hedeland M, Bondesson U, Knutson L, et al. (December 2009). "Enterohepatic disposition of rosuvastatin in pigs and the impact of concomitant dosing with cyclosporine and gemfibrozil".Drug Metabolism and Disposition.37(12): 2349–58.doi:10.1124/dmd.109.029363.PMID19773540.S2CID24783238.
  30. ^"Page 45 of FDA Drug Approval Package, Clinical Pharmacology Biopharmaceutics Review(s) (PDF)".U.S.Food and Drug Administration(FDA). 29 January 2004.Archivedfrom the original on 28 August 2016.Retrieved22 June2016.
  31. ^"International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 45"(PDF).World Health Organization. 2001. p. 50.Archived(PDF)from the original on 18 May 2016.Retrieved29 November2016.
  32. ^ab"Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Recommendation Statement".American Family Physician.95(2). January 2017.Archivedfrom the original on 3 August 2020.Retrieved9 May2022.
  33. ^"Affordable Care Act (ACA)-Essential Health Benefit (EHB) Zero Dollar Copay Preventive Medication List White Paper"(PDF).Arizona Department of Administration Human Resources.State of Arizona.Archived(PDF)from the original on 3 March 2022.Retrieved8 May2022.
  34. ^"Preventive care benefits for adults".Healthcare.gov.U.S. Centers for Medicare and Medicaid Services.Archivedfrom the original on 7 May 2022.Retrieved7 May2022.
  35. ^"Preventive Services Covered by Private Health Plans under the Affordable Care Act".Kaiser Family Foundation.4 August 2015.Archivedfrom the original on 2 May 2022.Retrieved7 May2022.
  36. ^"Affordable Care Act Implementation FAQs - Set 12".CMS.22 April 2013.Archivedfrom the original on 5 May 2022.Retrieved7 May2022.
  37. ^"SignatureValue Zero Cost Share Preventive Medications PDL"(PDF).Uhc.com.September 2021.Archived(PDF)from the original on 5 February 2022.Retrieved26 May2022.
  38. ^"COST COMPARISON CHARTS"(PDF).REGIONAL DRUG AND THERAPEUTICS CENTRE (NEWCASTLE). August 2018. Archived fromthe original(PDF)on 20 October 2018.Retrieved4 December2018.
  39. ^"Top 100 Drugs for Q2 2013 by Sales".Archivedfrom the original on 23 June 2018.Retrieved24 August2013.
  40. ^"Rosuvastatin - Drug Usage Statistics".ClinCalc.Retrieved14 January2024.
  41. ^"Core Data Sheet, Crestor Tablets"(PDF).AstraZeneca.June 17, 2003. Archived fromthe original(PDF)on May 8, 2005.RetrievedMarch 20,2005.- NOTE: this is provider-oriented information and should not be used without the supervision of a physician.
  42. ^Colman EC (8 February 2010).Supplement approval - CRESTOR (rosuvastatin calcium) Tablets(PDF)(Report). U.S.Food and Drug Administration(FDA). NDA 21366/S-016.Archived(PDF)from the original on 17 October 2012.Retrieved31 October2010.
  43. ^"Drug Approval Package: Crestor (Rosuvastatin Calcium) NDA #021366".U.S.Food and Drug Administration(FDA).29 January 2004.Archivedfrom the original on 6 August 2020.Retrieved15 March2020.
  44. ^"FDA Approves New Drug for Lowering Cholesterol".U.S.Food and Drug Administration(FDA). 12 August 2003. Archived fromthe originalon 7 February 2005.Retrieved20 March2005.
  45. ^"AstraZeneca's Crestor patent upheld;No generic competition until 2016".Delawareonline.com.Retrieved26 May2022.[permanent dead link‍]
  46. ^"Crestor Patent Upheld By US Court"(Press release).AstraZeneca.29 June 2010.Archivedfrom the original on 27 November 2020.Retrieved25 April2012– via PR Newswire.
  47. ^Berkrot B, Hals T (29 June 2010)."U.S. judge rules AstraZeneca Crestor patent valid".Reuters.Archivedfrom the original on 12 March 2016.Retrieved25 April2012.
  48. ^Starkey J (1 July 2010)."AstraZeneca patent upheld".The News Journal.Wilmington, Delaware. Archived fromthe originalon 31 January 2013.Retrieved25 April2012.(subscription required)
  49. ^"Crestor US patent upheld by Court of Appeals for the Federal Circuit".AstraZeneca(Press release). 14 December 2012.Archivedfrom the original on 9 July 2021.Retrieved9 July2021.
  50. ^"FDA approves first generic Crestor".U.S.Food and Drug Administration(FDA). 29 April 2016.Archivedfrom the original on 15 March 2020.Retrieved3 May2016.
  51. ^"Mylan Launches Generic Crestor Tablets"(Press release).Mylan.20 July 2016.Archivedfrom the original on 9 March 2021.Retrieved15 March2020– via PR Newswire.
  52. ^Horton R (October 2003)."The statin wars: why AstraZeneca must retreat".Lancet.362(9393): 1341.doi:10.1016/S0140-6736(03)14669-7.PMID14585629.S2CID39528790.
    McKillop T (November 2003)."The statin wars".Lancet.362(9394): 1498.doi:10.1016/S0140-6736(03)14698-3.PMID14602449.S2CID5300990.
  53. ^"Docket No. 2004P-0113/CP1".U.S.Food and Drug Administration(FDA).Archivedfrom the original on 2 July 2020.Retrieved2 July2020.
  54. ^Wolfe S (March 2015)."Rosuvastatin: winner in the statin wars, patients' health notwithstanding".BMJ.350:h1388.doi:10.1136/bmj.h1388.PMID25787130.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Rosuvastatin&oldid=1259807771"