Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States.
Purpose: Systemic exposure to rosuvastatin in Asian subjects living in Japan or Singapore is approximately twice that observed in Caucasian subjects in Western countries or in Singapore. This study was conducted to determine whether pharmacokinetic differences exist among the most populous Asian sub...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 71; no. 3; pp. 329 - 341 |
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| Autores principales: | , , , , , , , |
| Formato: | research tables/charts 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=103758300&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103758300 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: 103758300 101049391 10.1007/s00228-014-1800-0 NLM25630984 103758300 ppf: 329 ppct: 12 formats: fmt: @attributes: type: P tig: atl: Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States. aug: au: Birmingham, Bruce Bujac, Sarah Elsby, Robert Azumaya, Connie Zalikowski, Julie Chen, Yusong Kim, Kenneth Ambrose, Helen affil: AstraZeneca, Macclesfield, Cheshire UK sug: subj: Rosuvastatin Pharmacokinetics Pharmacogenetics White Persons Asians Race Factors Human United States Rosuvastatin Therapeutic Use Rosuvastatin Metabolism Polymorphism, Genetic Descriptive Statistics Hyperlipidemia Drug Therapy Male Female Analysis of Variance Confidence Intervals Genotype Food Intake Data Analysis Software Male Female ab: Purpose: Systemic exposure to rosuvastatin in Asian subjects living in Japan or Singapore is approximately twice that observed in Caucasian subjects in Western countries or in Singapore. This study was conducted to determine whether pharmacokinetic differences exist among the most populous Asian subgroups and Caucasian subjects in the USA. Method: Rosuvastatin pharmacokinetics was studied in Chinese, Filipino, Asian-Indian, Korean, Vietnamese, Japanese and Caucasian subjects residing in California. Plasma concentrations of rosuvastatin and metabolites after a single 20-mg dose were determined by mass spectrometric detection. The influence of polymorphisms in SLCO1B1 (T521>C [Val174Ala] and A388>G [Asn130Asp]) and in ABCG2 (C421>A [Gln141Lys]) on exposure to rosuvastatin was also assessed. Results: The average rosuvastatin area under the curve from time zero to time of last quantifiable concentration was between 64 and 84 % higher, and maximum drug concentration was between 70 and 98 % higher in East Asian subgroups compared with Caucasians. Data for Asian-Indians was intermediate to these two ethnic groups at 26 and 29 %, respectively. Similar increases in exposure to N-desmethyl rosuvastatin and rosuvastatin lactone were observed. Rosuvastatin exposure was higher in subjects carrying the SLCO1B1 521C allele compared with that in non-carriers of this allele. Similarly, exposure was higher in subjects carrying the ABCG2 421A allele compared with that in non-carriers. Conclusion: Plasma exposure to rosuvastatin and its metabolites was significantly higher in Asian populations residing in the USA compared with Caucasian subjects living in the same environment. This study suggests that polymorphisms in the SLCO1B1 and ABCG2 genes contribute to the variability in rosuvastatin exposure. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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