Stereospecific disposition of fluvastatin in streptozotocin-induced diabetic rats.
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.
Rocha
Adriana
A
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, Campus da Universidade de São Paulo, 14040-903, Ribeirão Preto, SP, Brazil.
Coelho
Eduardo Barbosa
EB
Lanchote
Vera Lucia
VL
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy; D005229:Fatty Acids, Monounsaturated / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use; D007211:Indoles / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin