ABSTRACT
OBJECTIVE： To study the effects of Wuzhi soft capsule and imatinib mesylate tablet on the pharmacokinetics of imatinib in rats. METHODS： The rats were divided into single administration group and consecutive administration group. The single administration group was divided into imatinib group one （ig administration of blank soybean oil+imatinib suspension 10 mg/kg）， low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group （ig administration of Wuzhi soft capsule solution 134， 268， 536 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given imatinib suspension intragastrically 30 min after intragastric administration of blank soybean oil/Wuzhi soft capsule solution. The consecutive administration group was divided into imatinib group two （ig administration of blank soybean oil+imatinib suspension 10 mg/kg）， Wuzhi soft capsule low-dose+imatinib group （ig administration of Wuzhi soft capsule solution 134 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given blank soybean oil/Wuzhi soft capsule solution intragastrically for consecutive 14 d， once a day； 30 min after last administration， ig imatinib suspension. About 100 μL blood was collected before imatinib， 0.5， 1， 2， 2.5， 3， 4， 5， 6， 8， 12， 24 and 36 h after medication. The plasma concentration of imatinib was determined by HPLC-MS/MS. The pharmacokinetic parameters were fitted by using DAS 2.0 software. RESULTS： After single administration， compared with imatinib group one， cmax， t1/2， AUC0-36 h and AUMC0-36 h in low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group were increased significantly （P＜0.05 or P＜0.01）. After consecutive administration， compared with imatinib group two， cmax， t1/2 and AUMC0-36 h of imatinib+low-dose of Wuzhi soft capsule group were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Single administration and consecutive administration of Wuzhi soft capsule influence the pharmacokinetics of imatinib， increase plasma concentration of imatinib and prolong half-time.
ABSTRACT
OBJECTIVE:To investigate the effect of Wuzhi soft capsule on the pharmacokinetics of sirolimus in rats. METH-ODS:Wistar rats were randomly divided into 5 groups,with 6 rats in each group. They were given very low-dose,low-dose,me-dium-dose and high-dose of Wuzhi soft capsule(67,134,268 and 536 mg/kg)ig or blank solvent,respectively;and then given si-rolimus 0.4 mg/kg. The blood 100 μl was sampled by capillary eyes before giving sirolimus(0 h)and 0.5,0.75,1,1.5,2,2.5, 3,4,6,8,12,24 and 36 h after giving sirolimus and put into edetic acid anticoagulation tube. Blood concentration of sirolimus was assayed by LC-MS/MS. The pharmacokinetic parameter was calculated by DAS 2.0 software using non-compartment model. RESULTS:The pharmacokinetic parameters of sirolimus in very low-dose,low-dose,medium-dose and high-dose groups and blank solvent group were cmax of(6.79±1.15),(17.40±3.13),(21.24±3.14),(22.06±4.82),(2.80±0.72)ng/ml;t1/2 of(11.01± 0.82),(12.20±2.02),(12.28±2.38),(12.36±0.73),(10.59±0.69)h;AUC0-∞ of(85.79±15.26),(162.18±41.75),(273.12± 73.69),(268.79±28.46),(36.72±3.01)ng·h/ml,respectively. Compared with blank solvent group,cmax and AUC0-∞ of sirolimus were all increased in very low-dose,low-dose,medium-dose and high-dose groups,but t1/2 changed slightly. CONCLUSIONS:Wu-zhi soft capsule can substantially enhance the absorption of sirolimus in rats.