title: Pharmacokinetics and pharmacodynamics of rosuvastatin in subjects with hepatic impairment.
abstract: OBJECTIVE
  To assess the effect of chronic hepatic impairment on rosuvastatin disposition, pharmacodynamic activity and tolerability.
  
  
  METHODS
  This was an open-label, non-randomised, parallel-group trial. Six subjects were enrolled in each of three hepatic-function strata: Child-Pugh class A (CP-A, mild impairment), Child-Pugh class B (CP-B, moderate impairment) and normal hepatic function; the latter two strata were age, weight, race, sex and smoking history matched. All subjects were given rosuvastatin 10 mg for 14 days.
  
  
  RESULTS
  In subjects with CP-A, and in four of six subjects with CP-B, rosuvastatin steady-state AUC(0-24) and C(max) were similar to subjects with normal hepatic function (geometric mean values 60.7 ng h/ml and 6.02 ng/ml, respectively). Two of six subjects with CP-B who had the highest CP scores (i.e. the highest degrees of hepatic impairment) had the highest AUC(0-24) (128 ng h/ml and 242 ng h/ml) and C(max) (23.4 ng/ml and 96.7 ng/ml) values. Low-density lipoprotein cholesterol (LDL-C) was decreased in all strata, but the response was more variable in the CP-B group. Rosuvastatin was well tolerated, and the safety profile was similar in subjects with hepatic impairment and normal hepatic function.
  
  
  CONCLUSIONS
  In most subjects with mild-to-moderate hepatic impairment, the steady-state pharmacokinetics of rosuvastatin were similar to subjects with normal hepatic function (more extensive hepatic impairment may increase systemic exposure to rosuvastatin), and most had LDL-C reductions similar to subjects with normal hepatic function.
authors.affiliation: AstraZeneca, R&D Lund, Experimental Medicine, SE-221 87 Lund, Sweden. steven.simonson@astrazeneca.com
authors.forename: S G
authors.initials: SG
authors.lastname: Simonson
authors.forename: P D
authors.initials: PD
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Mitchell
authors.forename: D W
authors.initials: DW
authors.lastname: Schneck
authors.forename: K C
authors.initials: KC
authors.lastname: Lasseter
authors.forename: M J
authors.initials: MJ
authors.lastname: Warwick
mesh_terms: D000328:Adult; D019540:Area Under Curve; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005464:Fluorobenzenes / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium