Dose Dependency of Fluvastatin Pharmacokinetics in Serum Determined by Reversed Phase HPLC
Open accessAbstract
Background: Fluvastatin is an inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, effectively lowering serum cholesterol concentrations. A high-performance liquid chromatography (HPLC) assay was developed that determined the pharmacokinetics of fluvastatin in healthy individuals after administration of 40 and 80 mg fluvastatin. Methods: The method was linear for serum concentrations between 10 ng/mL and 5,000 ng/mL, showing good coefficients of variations and sample stability. After administration of 40 mg fluvastatin, the mean values of the area under the serum concentration vs time curve (AUC), the maximum serum drug concentration (C,, 4 a), the time to reach CmaX (t.aJ, and the serum elimination half-life time were 528.5±8.8 ng/mL'h, 149.6 ±6.0 ng/mL, 60.0±30.0 minutes, and 108.0±7.9 minutes, respectively. The corresponding values for a dose of 80 mg fluvastatin were 1417.7 ±79.2 ng/mLh, 1024.7 +1085.1 ng/mL, 60.0 ±1.2 minutes, and 106.0 ±3.6 minutes, respectively. Doubling of the dose from 40 mg to 80 mg caused an overproportional increase of AUC and C max . Results and Conclusion: Results suggest that the measurement of fluvastatin serum concentrations by means of HPLC provides reliable data within the broad range of physiological serum concentrations. The pharmacokinetic data after administration of high doses (80 mg) showed an overproportional increase of AUC and Cm,,, suggesting a saturation of the hepatic first-pass effect. Thus, in patients treated with additional substances interfering with fluvastatin metabolism, fluvastatin serum concentrations should be analyzed.
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In patients taking FS for hypercholesterolemia, the serum concentration of FS falls into the intermediate range of 2-4 μM.
“In patients taking FS for the treatment of hypercholesterolemia, the serum concentration of FS falls into the intermediate range of 2–4 μM [14].”
From Inhibition of<i>Candida albicans</i>by Fluvastatin Is Dependent on pH (2009) · cites this paper as [14]
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- Authors
- Siekmeier, R., Lattke, P., Mix, C., Park, J.-W., & Jaross, W.
- Affiliations
- Federal Institute for Drugs and Medical Devices (DE)
- University Hospital Carl Gustav Carus (DE)
- Institute for Clinical Chemistry and Laboratory Medicine. University Hospital Carl Gustav Carus, Technical University, Dresden
- Consultant in Cardiovascular Medicine, Freital Hospital, Freital
- Venue
- Journal of Cardiovascular Pharmacology and Therapeutics
- Publisher
- SAGE Publications
- Published
- 2001-06
- Volume
- 6
- Issue
- 2
- Pages
- 137-145
- ISSN
- 1074-2484 (ISSN-L)
- 1940-4034
- OpenAlex
- W1973249883
- Cited by
- 30
- References
- 25
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 3 · 2016: 1 · 2013: 1
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cardiovascular Pharmacology and Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- fluvastatin, pharmacokinetics, dose dependency, statins, serum drug concentration, reversed-phase HPLC assay, hepatic first-pass metabolism, drug saturation, cholesterol lowering
- MeSH terms
- Fluvastatin, Administration, Oral, Anticholesteremic Agents, Chromatography, High Pressure Liquid, Dose-Response Relationship, Drug, Fatty Acids, Monounsaturated, Female, Humans, Indoles, Male, Middle Aged, Reproducibility of Results, Area Under Curve
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