OBJECTIVE

2

To study the effects of disodium cantharidinate on the pharmacokinetic behavior of capecitabine in rats.

METHODS

2

Rats were randomly divided into two control groups and two experimental groups with 6 rats in each group. Two control groups were intraperitoneally injected with normal saline， and two experimental groups were intraperitoneally injected with Disodium cantharidinate injection of 0.5 mL/kg， for 7 consecutive days. Eight days after medication， control group 1 and experimental group 1 were given capecitabine 5 mg/kg intragastrically， while control group 2 and experimental group 2 were given capecitabine 5 mg/kg intravenously. Blood samples were collected at different time points after administration. After extraction with ethyl acetate， the concentration of capecitabine in rat plasma was determined by UPLC-MS/MS method using tolbutamide as the internal standard. The pharmacokinetic parameters were calculated by DAS 2.0 software.

RESULTS

2

Compared with control group 1， MRT

0－∞

，

c

max

， AUC

0－30 h

， AUC

0－∞

and

F

of experimental group 1 were increased significantly， while CLz/F was decreased significantly （

P

＜0.01）. Compared with control group 2，

t

1/2

， MRT

0－30 h

， MRT

0-∞

， AUC

0－30 h

and AUC

0－∞

of experimental group 2 were increased significantly （

P

＜0.01）.

CONCLUSIONS

2

Disodium cantharidinate can increase the plasma exposure of capecitabine in rats， improve its oral bioavailability， prolong the average residence time， and reduce its clearance rate.