title: Dose dependency of fluvastatin pharmacokinetics in serum determined by reversed phase HPLC.
abstract: 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(max)), the time to reach C(max) (t(max)), and the serum elimination half-life time were 528.5 +/-358.8 ng/mL x h, 149.6 +/-56.0 ng/mL, 60.0 +/-30.0 minutes, and 108.0 +/-67.9 minutes, respectively. The corresponding values for a dose of 80 mg fluvastatin were 1417.7 +/-879.2 ng/mL x h, 1024.7 +/-1085.1 ng/mL, 60.0 +/-21.2 minutes, and 106.0 +/-73.6 minutes, respectively. Doubling of the dose from 40 mg to 80 mg caused an overproportional increase of AUC and C(max).
  
  
  CONCLUSIONS
  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 C(max), 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.
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technical University, Dresden.
authors.forename: R
authors.initials: R
authors.lastname: Siekmeier
authors.forename: P
authors.initials: P
authors.lastname: Lattke
authors.forename: C
authors.initials: C
authors.lastname: Mix
authors.forename: J W
authors.initials: JW
authors.lastname: Park
authors.forename: W
authors.initials: W
authors.lastname: Jaross
mesh_terms: D000284:Administration, Oral; D000924:Anticholesteremic Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results
chemical_list: D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin