title: Effects of silymarin on the pharmacokinetics of atorvastatin in diabetic rats.
abstract: The effect of silymarin (SMN) on the pharmacokinetics of atorvastatin in diabetic rats was evaluated. Male Wistar rats were assigned into two major groups and then sub-grouped according to the purposes of the study. The first major group was subdivided into three groups (n = 6) including control, non-treated diabetic and SMN-treated diabetic animals. In the first major group, metabolism of testosterone by the hepatic microsomes was studied. The second major group also was divided to three groups including atorvastatin-treated non-diabetic, atorvastatin-treated diabetic and diabetic animals which received both atorvastatin and SMN. To study the pharmacokinetics of atorvastatin, serum samples were collected at 0, 3, 6, 12 and 24 h after the atorvastatin administration. Pharmacokinetic parameters were calculated using non-compartmental model. Streptozotocin-induced diabetes resulted in a remarkable induction of testosterone hydroxylation as the V max for 6β-hydroxytestosterone production in the diabetic rats (77.3 ± 8.6 pM/min/mg) was significantly higher than that in the control animals (45.9 ± 5.9 pM/min/mg). Moreover, SMN-treated animals showed a significant (P < 0.05) reduction of V max (59.4 ± 6.1 pM/min/mg). Diabetes resulted in a significant reduction of AUC (control 6.98 ± 0.58 vs diabetic rats 4.35 ± 0.24 h mg/ml) and C max values (control 0.52 ± 0.03 vs diabetic group 0.33 ± 0.01 μg/ml), while the SMN-received group showed remarkable recovery of diabetes-reduced values of AUC and C max. These findings indicated that diabetes resulted in a significant up-regulation of microsomal enzyme activities. Moreover, as SMN could significantly regulate the enzyme activities and consequently the atorvastatin pharmacokinetics in diabetic rats, its regulative effect in a combination therapy is concluded.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University, P.O. Box 1177, Urmia, Iran, hassanmalekinejad@yahoo.com.
authors.forename: Hassan
authors.initials: H
authors.lastname: Malekinejad
authors.forename: Shirin
authors.initials: S
authors.lastname: Rokhsartalab-Azar
authors.forename: Sepideh
authors.initials: S
authors.lastname: Hassani-Dizaj
authors.forename: Shahin
authors.initials: S
authors.lastname: Alizadeh-Fanalou
authors.forename: Aysa
authors.initials: A
authors.lastname: Rezabakhsh
authors.forename: Amir
authors.initials: A
authors.lastname: Amniattalab
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D051544:Cytochrome P-450 CYP3A / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004347:Drug Interactions; D006538:Heptanoic Acids / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D011758:Pyrroles / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology*; D013311:Streptozocin; D013739:Testosterone / Q000378:metabolism
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D012838:Silymarin; D013739:Testosterone; D013311:Streptozocin; D000069059:Atorvastatin; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A