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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.

journal_name

Eur J Drug Metab Pharmacokinet

journal_title

European journal of drug metabolism and pharmacokinetics

authors

Malekinejad H,Rokhsartalab-Azar S,Hassani-Dizaj S,Alizadeh-Fanalou S,Rezabakhsh A,Amniattalab A

doi

10.1007/s13318-013-0166-5

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

311-20

issue

4

eissn

0378-7966

issn

2107-0180

journal_volume

39

pub_type

杂志文章

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