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.
ABSTRACT
Background Macular edema is one of the serious complications of central retinal vein occlusion (CRVO),and the present therapies are laser coagulation and intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs.Conbercept is humanized-monoclonal VEGF antibody and used for the treatment of retinal vascular diseases.However,fewer studies were focused on its application in macular edema secondary to CRVO.Objective The aim of this study was to compare the effectiveness and safety of conbercept with triamcinolone acetonide(TA)by intravitreal injections for macular edema secondary to CRVO. Methods A non-randomized controlled study was carried out under the approval of the informed consent of patients.Sixty eyes of 60 patients with macular edema secondary to CRVO were included in Weifang Yidu Central Hospital from March 2012 to August 2013.The eyes were divided into the conbercept group and TA group with 30 for each group.Conbercept and TA of 0.05 ml were intravitreally injected in different groups,and the best corrected visual acuity(BCVA),central macular thickness(CMT)measured by OCT,intraocular pressure(IOP)and relavant complications were examined before injection and 1 week,1 month,3 months and 6 months after injection.The treatment outcomes were compared intergrouply and along with time. Results The BCVA was evidently better in 1 week,1 month,3 months and 6 months after injection than that before injection both in conbercept group and TA group(all at P＜0.01),and the BCVA of TA group was better than that of conbercept group 1 week after injection(P＜0.05).The CMT values of Conbercept were(572.00± 100.01),(325.12±91.55),(280.00±92.37),(258.65 ±88.65),(300.00±87.64)μm,and those of TA group were(570.00± 102.21),(345.12±89.31),(290.00±80.27),(309.65 ±84.13)and(303.00±90.59)μm,and CMT value after injection was significantly lower in 1 week,1 month,3 months and 6 months after injection than that before injection both in the conbercept group and the TA group(all at P＜0.05),and CMT value was evidently reduced in the conbercept group compared with the TA group 3 months after injection(P＜0.05).The IOP was(15.20±3.52),(21.20±3.80),(26.40±4.00),(23.60±3.73)and(21.50±3.27)mmHg in the TA group before injection and 1 week,1 month,3 months and 6 months after injection,showing significnatly elavation after injection(all at P＜0.05),and the IOP at different time points was higher in the TA group than that in the conbercept group(all at P＜0.05).However,there was no considerable change of IOP before and after injection in conbercept group(all at P＜0.05). Conelutions Both conbercept and TA are effective for macular edema secondary to CRVO by intravtreal injection.Compared with TA,conbercept is much safer because of less risk of IOP rising after intravtreal injection.