title: Modeling of the LDL cholesterol-lowering effect of atorvastatin in Korean dyslipidemic patients and non-patient volunteers.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology, Yonsei University Severance Hospital, Seoul, Korea.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Oh
authors.forename: Sang-Hak
authors.initials: SH
authors.lastname: Lee
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Park
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Park
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Chung
mesh_terms: D000328:Adult; D044466:Asian People; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003198:Computer Simulation; D003661:Decision Support Techniques; D015536:Down-Regulation; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011758:Pyrroles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D056910:Republic of Korea / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin