Renal dysfunction does not alter the pharmacokinetics or LDL-cholesterol reduction of atorvastatin

J Clin Pharmacol. 1997 Sep;37(9):816-9. doi: 10.1002/j.1552-4604.1997.tb05629.x.

Abstract

The objective of this study was to determine the effects of renal dysfunction on the steady-state pharmacokinetics and pharmacodynamics of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Nineteen subjects with calculated creatinine clearances ranging from 13 mL/min to 143 mL/min were administered 10 mg atorvastatin daily for 2 weeks. Pharmacokinetic parameters and lipid responses were analyzed by regression on calculated creatinine clearance. Correlations between steady-state atorvastatin pharmacokinetic or pharmacodynamic parameters and creatinine clearance were weak and, in general, did not achieve statistical significance. Although the elimination rate constant, lambda z (0.579), was significantly correlated with creatinine clearance, neither maximum plasma concentration (Cmax, -0.361) nor oral clearance (Cl/F, 0.306) were; thus, steady-state exposure is not altered. Renal impairment has no significant effect on pharmacodynamics and pharmacokinetics of atorvastatin.

MeSH terms

  • Adult
  • Aged
  • Atorvastatin
  • Cholesterol, LDL / blood*
  • Female
  • Heptanoic Acids / pharmacokinetics*
  • Heptanoic Acids / pharmacology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Male
  • Middle Aged
  • Pyrroles / pharmacokinetics*
  • Pyrroles / pharmacology
  • Renal Insufficiency / metabolism*

Substances

  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin