Impact of ABCG2 and SLCO1B1 polymorphisms on pharmacokinetics of rosuvastatin, atorvastatin and simvastatin acid in Caucasian and Asian subjects: a class effect?
Purpose: Systemic exposure to rosuvastatin is approximately double that of Caucasians in Asian subjects. We investigated whether this pattern of increased exposure exists for other statins. Methods: Plasma exposure following single-dose rosuvastatin 20 mg, atorvastatin 40 mg or simvastatin 40 mg was...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 71; no. 3; pp. 341 - 356 |
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| Autores principales: | , , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Mar2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103758294&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103758294 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Mar2015 vid: 71 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 103758294 101049390 10.1007/s00228-014-1801-z NLM25673568 103758294 ppf: 341 ppct: 15 formats: fmt: @attributes: type: P tig: atl: Impact of ABCG2 and SLCO1B1 polymorphisms on pharmacokinetics of rosuvastatin, atorvastatin and simvastatin acid in Caucasian and Asian subjects: a class effect? aug: au: Birmingham, Bruce Bujac, Sarah Elsby, Robert Azumaya, Connie Wei, Cheryl Chen, Yusong Mosqueda-Garcia, Rogelio Ambrose, Helen affil: AstraZeneca, Macclesfield UK sug: subj: Polymorphism, Genetic Rosuvastatin Pharmacokinetics Atorvastatin Pharmacokinetics Simvastatin Pharmacokinetics Asians White Persons Race Factors Human Descriptive Statistics Confidence Intervals Statins Blood Data Analysis Software Randomized Controlled Trials Crossover Design Male Female Analysis of Variance Adult Middle Age Analysis of Covariance Funding Source California Hyperlipidemia Drug Therapy Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: Purpose: Systemic exposure to rosuvastatin is approximately double that of Caucasians in Asian subjects. We investigated whether this pattern of increased exposure exists for other statins. Methods: Plasma exposure following single-dose rosuvastatin 20 mg, atorvastatin 40 mg or simvastatin 40 mg was studied in Chinese, Japanese and Caucasian subjects. Plasma concentrations were determined using LC-MS methods. Impact of polymorphisms in SLCO1B1 (T521>C and A388>G) and in ABCG2 (C421>A) on exposure to rosuvastatin, atorvastatin, simvastatin and simvastatin acid was assessed. Results: Relative to Caucasians, geometric mean area under the curve from time zero to time of last quantifiable concentration was 86 % (90 % confidence interval (CI), 51-130 %) and 55 % (26-91 %) higher for rosuvastatin in Chinese and Japanese subjects, respectively, 53 % (25-88 %) and 69 % (37-108 %) higher for atorvastatin, 23 % (0-52 %) and 12 % (−0.9-39 %) higher for simvastatin and 28 % (5-56 %) and 34 % (10-64 %) higher for simvastatin acid. Geometric mean maximum drug concentration was also proportionally higher for each statin. Polymorphisms in SLCO1B1 T521>C or ABCG2 C421>A were associated with higher exposure to rosuvastatin, atorvastatin and simvastatin acid (but not simvastatin) within a population, but only the ABCG2 C421>A polymorphism contributed towards between-population exposure differences. In individuals carrying wild-type alleles for both SLCO1B1 and ABCG2, area under the plasma concentration-time curve (AUC) still appeared to be higher for rosuvastatin, atorvastatin and simvastatin acid in Chinese and Japanese subjects compared with Caucasians, respectively. Conclusion: Increased exposure to statins in Asian subjects versus Caucasians may represent a more general class phenomenon than previously recognized. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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