Renal Dysfunction Does Not Alter the Pharmacokinetics or LDL‐Cholesterol Reduction of Atorvastatin

@article{Stern1997RenalDD,
  title={Renal Dysfunction Does Not Alter the Pharmacokinetics or LDL‐Cholesterol Reduction of Atorvastatin},
  author={Ralph H. Stern and B-B Yang and M. Horton and S Moore and Robert B. Abel and Stephen C. Olson},
  journal={The Journal of Clinical Pharmacology},
  year={1997},
  volume={37}
}
  • R. Stern, B-B Yang, S. Olson
  • Published 1 September 1997
  • Biology, Medicine, Chemistry
  • The Journal of Clinical Pharmacology
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… 
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References

SHOWING 1-9 OF 9 REFERENCES
Single‐dose pharmacokinetics of 14C‐lovastatin in chronic renal failure
TLDR
Results indicate that patients with severe renal dysfunction have altered elimination kinetics of lovastatin, and total inhibitors in plasma and total radioactivity were similarly elevated in patients with chronic renal failure.
Single‐Dose Pharmacokinetics of Pravastatin and Metabolites in Patients with Renal Impairment
TLDR
This single‐dose study demonstrates that pravastatin pharmacokinetics were not affected in patients with renal impairment, probably because of its dual route of elimination.
Effect of Age and Gender on Pharmacokinetics of Atorvastatin in Humans
TLDR
It is unclear whether these age‐ and gender‐related differences in the pharmacokinetics of atorvastatin will be clinically important, and results of subsequent safety and efficacy trials should help clarify the clinical significance of these pharmacokinetic differences.
Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor.
TLDR
Atorvastatin was well tolerated by hyperlipidemic patients, had an acceptable safety profile, and provided greater reduction in cholesterol than other previously reported HMG-CoA reductase inhibitors.
Drug Dosing in Renal Insufficiency
  • R. Talbert
  • Medicine, Biology
    Journal of clinical pharmacology
  • 1994
Drug dosing in renal insufficiency needs to be individualized whenever possible to optimize therapeutic outcomes and to minimize toxicity. Although a number of published tables that provide dosing
Effect of age and gender on atorvastatin pharmacokinetics in humans
  • J Gun Pharmacol
  • 1996
Development and validation of an enzyme inhibition assay for quantitation of CI-981 in human plasma labstracti
  • Pharm Res
  • 1993
Single-dose pharmacokinetics of ‘4C-lovastatin in chronic renal failure
  • Gun Pharmacol Ther 1991;50:437-441
  • 1991