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 24h 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±8.6pM/min/mg) was significantly higher than that in the control animals (45.9±5.9pM/min/mg). Moreover, SMN-treated animals showed a significant (P<0.05) reduction of V max (59.4±6.1pM/min/mg). Diabetes resulted in a significant reduction of AUC (control 6.98±0.58 vs diabetic rats 4.35±0.24hmg/ml) and C max values (control 0.52±0.03 vs diabetic group 0.33±0.01μg/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.