The Preparation Of Fenbendazole-Praziquantel Suspension And Its Pharmacokinetic Studies In Dogs

The research relates to pharmaceutical compostions for veterinary use containing fenbendazole and praziquantel as the active pharmaceutical ingredient in aqueous suspensions.Good resuspendable aqueous suspensions contained an appropriate amount of necessary excipients such as suspending agents, wetting agent, aseptic and so on.The research was designed with orthogonal design to select the best prescription, and the stabile suspension acquired with dispersion method by aseptic manipulation. The stability and pharmacokinetics of this preparation in dogs were also studied in the paper. The research on the stability of fenbendazole-praziquantel suspension included intensive light test, the accelerated test and the long-term test. The results showed that it is stable under temperature and humidity, but it is a little sensitive under light. Its content was lower under intensive light after a period of time. However, conserving fenbendazole-praziquantel suspension under tight light for a period of time, the active ingredient of fenbendazole and praziquantel and its color was basically no change.Nine clinically healthy dogs that initial weight is 9.81±1.6 kg were randomly divided into three groups: group A, group B, group C. Nine dogs received a dose of 25mg/kg of fenbendazole and praziquantel suspension orally and 25mg/kg of fenbendazole tablets orally and 2.5 mg/kg praziquantel tablets orally in a three-way crossover design. The experiments were performed with one week between each administration. Blood samples were collected in different time set before the experiment.The collected blood samples were determined by HPLC-MS/MS. Fenbendazole and praziquantel concentration-time data analyzed by Win Nonlin5.2.1 pharmacokinetic program according to a non-compartment model. The main pharmacokinetic parametersof fenbendazole for fenbendazole-praziquantel suspension,were as follows: AUC0-t 1187.16±383.90 h·ng/m L, Cmax 180.57±56.09 ng/m L, Tmax 5.44 ±1.51 h, MRT 7.90±1.22,; The main pharmacokinetic parameters of praziquantel for fenbendazole-praziquantel suspension,were as follows :AUC0-t 715.1±180.25 h·ng/m L, Cmax 198.44±74.39 ng/m L, Tmax 2.11 ±0.78 h, MRT 3.62±0.70 h. The main pharmacokinetic parameters of fenbendazole for fenbendazole tablets were as follows: AUC0-t 1017.81±363.07 h·ng/m L, Cmax 207.82±67.68 ng/m L, Tmax 3.00 ±0.71 h, MRT 4.95±0.74 h. The main pharmacokinetic parameters of praziquantel for praziquantel tablets were as follows: AUC0-t 620.04±157.65 h·ng/m L, Cmax 245.16±68.26 ng/m L, Tmax 1.67 ±0.50 h, MRT 2.63±0.31 h.In conclusion, the fenbendazole-praziquantel suspension had good stability, compared with the single drug administration, The fenbendazole and praziquantel of fenbendazole--praziquantel suspension was absorbed slowly afer oral administraton, the Tmax was significantly dealayed, the mean retention time(MRT) was prolonged,the Cmax was reduced, the effective blood drug concentration maintenance time was prolonged, the result showed the fenbendazole-praziquantel suspension had certain sustained release effects,this contributes to the insect-resistance activity; The bioavailability of fenbendazole--praziquantel suspension in dogs were respectively 115.57%±7.88% for fenbendazole and 115.57%±7.88% for praziquantel,this showed fenbendazole--praziquantel suspension was relatively absorbed easily.The successful development of fenbendazole--praziquantel suspensions could provide broader prospects for veterinary clinical application.