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Cited by 204Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismPharmacogenetics and Drug Metabolism

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Multiple-dose pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an inhibitor of HMG-CoA reductase, in healthy subjects

Cilla, Donald D., Whitfield, Lloyd R., Gibson, Donald M., Sedman, Allen J., Posvar, Edward L.·1996·Clinical Pharmacology & Therapeutics
DOI 10.1016/s0009-9236(96)90218-0
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Abstract

This study examined the pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an investigational inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, in 50 healthy subjects by means of a randomized, double-blind parallel-group design. Volunteers received rising single and multiple doses of 0.5 to 80 mg/day atorvastatin (40 subjects) or placebo (10 subjects). The drug was administered once or twice daily for 14 days. Atorvastatin was well tolerated by healthy subjects. The most common adverse events reported after atorvastatin-headache and nausea-occurred as frequently after placebo. Atorvastatin peak concentration and area under the plasma concentration-time curve (AUC) values increased more than proportionally with atorvastatin dose after both single and multiple drug doses. The extent of atorvastatin absorption (AUC) was similar after once- or twice-daily drug administration. Steady-state drug concentrations were achieved by the third day of drug dosing. Mean elimination half-life values ranged from 11 to 24 hours. Atorvastatin accumulation was approximately 1.5- and 3.0-fold after once- and twice-daily administration, respectively. Atorvastatin produced dose-related reductions in total cholesterol and low-density lipoprotein cholesterol that were similar after once- and twice-daily drug administration. Reductions in mean total cholesterol and low-density lipoprotein cholesterol values ranged from 13% and 22% (2.5 mg/day) to 45% and 58% (80 mg/day), respectively (p < or = 0.0013 in comparison with placebo and with baseline over this dose range). In summary, atorvastatin doses of up to 80 mg/day were well tolerated and had significant cholesterol-lowering effects.

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Crossref · 10.1016/s0009-9236(96)90218-0

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Research works printed but not linked: 6

  1. Shaw M. K., 1990, FASEB J, 4, A533
  2. Krause B. R., 1993, FASEB J, 7, A567
  3. Shum Y. Y., 1993, Pharm Res, 10, S-415
  4. Levy R. I., 1993, Circulation, 87, 45
  5. Davignon J., 1992, Can J Cardiol, 8, 843
  6. Leitersdorf E., 1993, Circulation, 87, 35

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Metadata

Authors
Cilla, D. D., Whitfield, L. R., Gibson, D. M., Sedman, A. J., & Posvar, E. L.
Corresponding author
Sedman, Allen J.
Venue
Clinical Pharmacology & Therapeutics
Publisher
Wiley
Published
1996-12
Volume
60
Issue
6
Pages
687-695
ISSN
  • 0009-9236 (ISSN-L)
  • 1532-6535
DOI
10.1016/s0009-9236(96)90218-0
OpenAlex
W1971242943
Cited by
204
References
8
Citations by year
2026: 1 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 2 · 2021: 7 · 2020: 5 · 2019: 7 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 8 · 2014: 11 · 2013: 4 · 2012: 9
FWCI
4.99
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
atorvastatin, statins, multiple-dose pharmacokinetics, pharmacodynamics, dose proportionality, LDL cholesterol lowering, total cholesterol, elimination half-life, drug accumulation, adverse events, drug safety, healthy volunteers
MeSH terms
Atorvastatin, Acyl Coenzyme A, Adult, Anticholesteremic Agents, Cholesterol, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Enzyme Inhibitors, Female, Half-Life, Heptanoic Acids, Humans, Male, Middle Aged, Pyrroles, Reference Values, Linear Models, Least-Squares Analysis, Area Under Curve

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