Pharmacokinetic Study on Single and Multiple Administration of Gefitinib Emulsion in Rats / 中国药房

ABSTRACT

ABSTRACT OBJECTIVE：To study pharmacokinetic characteristics of single dose and multiple dose administration of Gefitinib emulsion in rats. METHODS：The rats were divided into single administration group and multiple administration group. Single administration group was subdivided into Gefitinib raw medicine group（50 mg/kg，i.g.）and Gefitinib emulsion group（50 mg/kg，i.g.），with 6 rats in each group，gavage once. Multiple administration group were subdivided into Gefitinib raw medicine group （50 mg/kg）and Gefitinib emulsion group（50 mg/kg），with 8 rats in each group；they were given relevant medicine intragastricaly for consecutive 7d，once a day. 0.3 mL blood of rats in Gefitinib raw medicine group was taken before medication and 1，2，2.5， 3，3.5，3.75，4，4.25，4.5，6，8，12 and 24 h after medication；0.3 mL blood of rats in Gefitinib emulsion group was taken before medication and 2，4，6，8，9，10，11，12，13，14，16，24，36 and 48 h after administration（Multiple administration group is after 7 d of administration）. HPLC method was used to determine the plasma concentration of gefitinib in rat，and plasma concentration-time curves were drawn. Pharmacokinetic parameters were fitted by using DAS 2.0 software. RESULTS：After single administration，compared with the tmax（[ 2.67±0.75）h]，MRT0-24 h （[ 8.68±0.91）h]，MRT0- ∞ （[ 14.20±3.45）h] of Gefitinib raw medicine group，tmax （[ 8.33±4.41）h]，MRT0-48 h （[ 15.00±1.60）h]，MRT0-∞ （[ 17.60±2.66）h] of Gefitinib emulsion group were increased significantly（P＜0.05）. After multiple administration，compared with the tmax （[ 6.79±3.75）h]，AUC0-48 h （[ 41.10±8.92） mg·h/L]，Vz/F [（16.30±5.45）L/kg]，CLz/F [（0.94±0.19） L/（h·kg）]，MRT0-48 h （[ 10.10 ± 0.36） h] of Gefitinib raw medicine group，Vz/F [（44.20±30.3）L/kg]，CLz/F[（1.89± 1.56） L/（h·kg）]，MRT0-48 h （[ 16.20 ± 2.52） h] of Gefitinib emulsion group were increased significantly （P＜0.05） AUC0-48 h （[ 38.70±26.20）mg·h/L] was decreased significantly （P＜0.05），and tmax （[ 10.40±3.25）h] was increased，without statistical significance. CONCLUSIONS： Compared with Gefitinib raw medicine，single and multiple administration of Gefitinib emulsion can effectively prolong the peak time，the results of this study can provide reference for new delivery system study of Gefitinib.