Stereospecific disposition of fluvastatin in streptozotocin-induced diabetic rats

Can J Physiol Pharmacol. 2002 Nov;80(11):1071-5. doi: 10.1139/y02-136.

Abstract

The study reports on the stereoselective pharmacokinetics of fluvastatin, a racemic mixture of (-)-(3S,5R)- and (+)-(3R,5S)-enantiomers, in streptozotocin-induced diabetic rats. Wistar (control) and streptozotocin-induced diabetic rats (n = 6/time point) received by oral gavage racemic fluvastatin (5 mg/kg), and blood samples were collected until 24 h. The enantiomers were analysed by chiral HPLC with fluorescence detection. The pharmacokinetic parameters were analysed by Wilcoxon and Mann-Whitney tests. The results are reported as means (95% CI). The following differences (p < 0.05) were observed between the control and diabetic groups, respectively: maximum plasma concentration (Cmax) of (-)-(3S,5R), 410.0 (310.0-510.0) versus 532.6 (463.5-601.8) ng x mL(-7); area under the plasma concentration versus time curve (AUC(0-infinity)) for (-)-(3S,5R), 4342A (3,775.7-4,909.0) versus 3025.2 (2,218.9-3,831.5) ng x h x mL(-1); apparent total clearance (Cl/f) of (-)-(3S,5R), 0.6 (0.5-0.7) versus 0.9 (0.6-1.1) L x h(-1) x kg(-1); AUC(0-infinity) for (+)-(3R,5S), 493.5 (376.9-610.1) versus 758.5 (537.1-980.0) ng x h x mL(-1); and Cl/f of (+)-(3R,5S), 5.3 (3.9-6.8) versus 3.5 (2.6-4.4) L x h(-1) x kg(-1). Streptozotocin-induced diabetes in rats alters the pharmacokinetics of fluvastatin in a stereoselective manner.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / blood*
  • Diabetes Mellitus, Experimental / drug therapy
  • Fatty Acids, Monounsaturated / blood*
  • Fatty Acids, Monounsaturated / chemistry
  • Fatty Acids, Monounsaturated / therapeutic use
  • Fluvastatin
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / blood
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Indoles / blood*
  • Indoles / chemistry
  • Indoles / therapeutic use
  • Male
  • Rats
  • Rats, Wistar
  • Stereoisomerism

Substances

  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Fluvastatin