Triclosan Pharmacokinetic In The Knee: Injecting Antibacterial Emulsions With Triclosan And Hydrogel In The Injured Knee Of Rabbits

Objective:Dispense four species of antibacterial emulsions such as Triclosan,Triclosan-Hydrogel Acid,Triclosan-Chitosan and Triclosan-Hydrogel Acid/Chitosan using hydrogel such as Hydrogel Acid,Chitosan and Hydrogel Acid/Chitosan,then inject them into joint cavity of the injured knee of rabbits:①to compare the concentration and time course of triclosan joint cavity after the injection,②to compare the triclosan pharmacokinetic in the blood of rabbits after the injection,③to investigate the diversity of fasting plasma glucose change.Methods:The experiment was conducted in the experiment center of PLA general hospital between December 2008 and May 2009.①Dispense antibacterial emulsions:confecting Triclosan emulsions,then getting new emulsions separately after swing in with hydrogel such as Hydrogel Acid,Chitosan and Hydrogel Acid/Chitosan.②Induction of experimental traumatic Arthritis:takes the knee outside approach of the rabbit after anaesthetize,and a bone window was made at the patellofemoral joint,which is deep enough to subchondral bone with circle section of 4.5 mm diameter.Both knees of rabbits served as self-control without splinting after surgery③Grouping:group A(controled group) involves triclosan,cremophor;group B(Triclosan-Hydrogel Acid group) involves triclosan,hydrogel acid and cremophor;group C(Triclosan-Chitosan group), involves triclosan,chitosan and cremophor;group D(combined hydrogel group) involves triclosan,hydrogel acid,chitosan and cremophor.④Getting joint cavity samples and outcome measuring:24(48 knees) rabbits of the same brood were divided into 4 groups(A,B,C,D) randomly,with 6(12 knees) rabbits in each group.6 days after both knees surgery injecting antibacterial emulsions at the same time.In each group choosing 3 knees each time at 6,12,24,48hours after instillation,the drug was analyzed with high pressure liquid chromatogram (HPLC),to compare the concentration and time course oftriclosan in in joint cavity after the injection.⑤Getting blood samples and outcome measuring:24 New Zealand rabbits of the same brood were divided into 4 groups(A,B,C,D) randomly,with 6 rabbits in each group,injecting antibacterial emulsions 6 days after left knee surgery.Blood collection at 6,12,24,48,72,96hours after instillation,the drug was analyzed with high pressure liquid chromatogram (HPLC),to compare the concentration and time course oftriclosan in the blood after the injection。⑥Measuring fasting plasma glucose:30 rabbits of the same brood were divided into 5 groups(A,B,C,D,E) randomly,with 6 rabbits in each group,injecting antibacterial emulsions 6 days after left knee surgery. injecting emulsions into group A/B/C/D.injecting physiological saline into group E(blank group).Blood was collected before instillation as well as at 0,6,12,24, 48,72,96 hours after instillation and measured fasting plasma glucose to investigate the diversity of fasting plasma glucose change.Results:1.To compare the triclosan pharmacokinetic in joint cavity1.1 To compare the time course of triclosan in joint cavityThe time course resulted in a lower level in controlled group and combined hydrogel group compared to group Tri-HA and group Tri-CH.(P＜0.05)1.2 To compare the peak concentration of triclosan in joint cavity①The peak concentration of controlled group(8.601±0.067mg/ml) resulted in a higher level than other groups.(P＜0.05)②The peak concentration of group Tri-HA(0.751±0.018mg/ml) resulted in a higher level than group Tri-CH(6.003±0.155mg/ml)and combined hydrogel group(7.026±0.137mg/ml),especially for controlled group.(P＜0.05) 1.3 To compare the average concentration of triclosan in joint cavity①The average concentration of controlled group(5.141±0.056mg/ml) resulted in a higher level than other groups.(P＜0.05)②The average concentration of group Tri-CH(3.687±0.018mg/ml) resulted in a higher level than group Tri-HA(3.652±0.155mgm/L)and combined hydrogel group(4.341±0.127mg/ml),especially for controlled group (P＜0.05)。2.To compare the triclosan pharmacokinetic in the bloodTriclosan was checked out in each group,time course resulted in a lower level in controlled group and combined hydrogel group compared to group Tri-HA and group Tri-CH.(P＜0.05) Average concentration resulted in a higher level in controlled group and combined hydrogel group compared to group Tri-HA and group Tri-CH.(P＜0.05).Average concentration in combined hydrogel group was significantly higher than other groups(P＜0.05),time course was minimal of all.Among group Tri-HA and group Tri-CH,Average concentration in group Tri-CH,was significantly lower than other groups (P＜0.05),time course was maximal of all.3.To compare the diversity of fasting plasma glucose change.3.1 To compare the diversity of fasting plasma glucose increase.①To compare the maximum decrease.The maximum decrease of fasting plasma glucose in controlled group(1.501±0.137 mmol/L) and combined hydrogel group(1.034±0.067mmol/L)resulted in a significantly higher level than group Tri-HA(0.661±0.0188mmol/L),group Tri-CH(0.703±0.155mmol/L)and blank group(0.624±0.155retool/L).(P＜0.05)②To compare the average decrease.The average decrease of fasting plasma glucose in group Tri-HA(0.353±0.018mmol/L) resulted in a lower level than group Tri-CH(0.346±0.045mmol/L) and blank group(0.364±0.055 retool/L),but there was on significance among them.(P＞0.05) 3.2 To compare the diversity of fasting plasma glucose decrease.①To compare the maximum increase.The maximum increase of fasting plasma glucose in controlled group(1.601±0.137mmol/L) and combined hydrogel group(1.026±0.067mmol/L) resulted in a significantly higher level than group Tri-CH(0.803±0.155mg/L),group Tri-HA(0.751±0.018mmol/L) and blank group(0.813±0.155mmol/L).(P＜0.05)②To compare the average increase.The average increase of fasting plasma glucose in group Tri-HA(0.351±0.018mmol/L) resulted in a lower level than group Tri-CH(0.357±0.022mmol/L)and blank group(0.386±0.045mmol/L),but there was on significance among them.(P＞0.05)Conclusions:1 Triclosan-Hydrogel Acid and Triclosan-Chitosan emulsions achieve lower triclosan level in joint cavity and longer time course compared to Triclosan emulsions as well as combined hydrogel emulsions.But just maintain short time, repeated injection was indispensable.2.Triclosan-Hydrogel Acid and Triclosan-Chitosan emulsions achieve lower triclosan level inblood,and there was on significance abnormal change of fasting plasma glucose.3 Triclosan-Hydrogel Acid emulsions achieve longer time course in joint cavity compared to Triclosan-Chitosan emulsions,it ismore suitablefor clinicaluse.