title: Renal dysfunction does not alter the pharmacokinetics or LDL-cholesterol reduction of atorvastatin.
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.
authors.affiliation: Department of Clinical Pharmacology, Parke-Davis Pharmaceutical Research Division of Warner-Lambert Company, Ann Arbor, Michigan, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Stern
authors.forename: B B
authors.initials: BB
authors.lastname: Yang
authors.forename: M
authors.initials: M
authors.lastname: Horton
authors.forename: S
authors.initials: S
authors.lastname: Moore
authors.forename: R B
authors.initials: RB
authors.lastname: Abel
authors.forename: S C
authors.initials: SC
authors.lastname: Olson
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006538:Heptanoic Acids / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000493:pharmacokinetics* / Q000494:pharmacology; D051437:Renal Insufficiency / Q000378:metabolism*
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin