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Modeling of the LDL cholesterol-lowering effect of atorvastatin in Korean dyslipidemic patients and non-patient volunteers.

Authors
 Eun Sil Oh ; Sang-Hak Lee ; Jae-Yong Chung ; Kyungsoo Park ; Min Soo Park 
Citation
 International Journal of Clinical Pharmacology and Therapeutics, Vol.50(9) : 647~656, 2012 
Journal Title
 International Journal of Clinical Pharmacology and Therapeutics 
ISSN
 0946-1965 
Issue Date
2012
Abstract
OBJECTIVE: The aim of this study was to develop a longitudinal pharmacodynamic model describing the time-courses of low-density lipoprotein cholesterol (LDL) profiles during and after atorvastatin treatment in Korean dyslipidemic patients and non-patient volunteers. METHODS: 15 dyslipidemic patients and 11 non-patient volunteers with no prior therapy participated in a parallel, 2-step dose escalation study. Subjects received atorvastatin doses ranging from 10 to 80 mg for 42 days (dyslipidemic patients) or 10 mg for 21 days (non-patient volunteers). Plasma samples were collected before and during the treatment period and up to 2 weeks after the last administration. A population pharmacodynamic model was built using the NONMEM software package. An indirect response model consisting of production in hepatocyte and elimination from plasma stimulated by atorvastatin described the LDL time-course. RESULTS: The typical population value of the estimated dose producing 50% of maximal stimulation on LDL elimination (SD50) for dyslipidemic patients was 11.9 mg, which was about 6 times higher than that of non-patient volunteers (2.0 mg). CONCLUSION: A longitudinal population pharmacodynamic model for the LDL-lowering effect of atorvastatin in both dyslipidemic patients and non-patient volunteers was developed. This could help guide optimal therapies according to the target population.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/90464
DOI
10.5414/CP201699
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Pediatrics
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
Yonsei Authors
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Link
 http://www.dustri.com/index.php?id=98&artId=9968
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