Pharmacokinetics And Histopathology Of Praziquantel In Chinemys Reevesiis By Intragastric Administration

In order to provide scientific guidance for safe and effective use of praziquantel in clinical deworming of turtles,this experiment aimed to study the pharmacokinetic characteristics,adverse reaction evaluation and tissue toxicology of praziquantel in C.reevesiis.It was divided into 4 groups,each group consisting of 3 healthy adult C.reevesiis as parallel.The dynamic characteristics of absorption and metabolism of praziquantel in C.reevesiis were studied by analyzing and comparing the main pharmacokinetic parameters with different sexes,different doses and different times of administration.At the same time,safety of praziquantel on C.reevesiis was evaluated,and adverse reaction grade was designed according to the degree of poisoning,so as to evaluate the adverse reactions.The dying or just-dead poisoning turtle was immediately dissected and observed,the tissues and organs were separated,paraffin sections were taken for HE staining,and histopathological examination was performed under the microscope.The pharmacokinetic study showed that the drug-time data of praziquantel in C.reevesiis were consistent with the one-compartment open model and showed a bimodal effect.Main pharmacokinetic parameters:test group I?30mg/kg bw,single,female?:T_max=15.949 h,C_max=0.615 ug/mL,AUC=26.664?g/mL·h;test group II?30mg/kg b.w,single,male?:T_max=74.857 h,C_max=0.592?g/mL,AUC=123.427?g/mL·h;test group III?15 mg/kg bw,single,male?:T_max=75.523 h,C_max=0.234?g/mL,AUC=48.760?g/mL·h;test group IV?10 mg/kg bw,3 times,female?:T_max=14.161 h,C_max=0.303?g/mL,AUC=15.726?g/mL·h.The peak time T_max,absorption rate Ka and elimination rate Kel of the male C.Reevesiis were smaller than that of female tortoise.The C_maxax and AUC of the praziquantel in C.reevesiis increased with the dose,but the peak time,the absorption and metabolism rate are basically the same.The peak time T_maxax of praziquantel in C.reevesiis administered by intragastric was only related to gender,but the absorption and metabolism rate of praziquantel was higher than that of male tortoise.When the doses were the same,Ka and MRT of the multiple administration group were larger than that of the single administration group,and Kel was smaller,indicating that the multiple intervals of reasonable interval can increase the absorption level and prolong the effective blood concentration time.The adverse reaction evaluation results showed that there were strong adverse reactions in the test group I-III,and the symptoms were basically same.The main characteristics were decreased feeding ability,hind limb dyskinesia,mental state deterioration,and severe death.The evaluation grades of the test group I was respectively 4,1,and 3.The test group II was respectively,4,2,and 3.The test group III was 4,2,and 4 respectively.The test group IV was 1,0,0respectively,only one had adverse reaction of grade 1 on the 8th day after administration?other pathogenic factors are not excluding?,the other two had no adverse reactions.Anatomical and histopathological observations showed that the kidneys,liver and other organ tissues of the poisoned turtles in the test group I-III had different degrees and types of lesions,of which kidney tissue was the most serious.It can be sorted into:kidney tissue>liver tissue>spleen tissue,pancreatic tissue>heart tissue,lung tissue>stomach tissue,intestinal tissue>muscle tissue,adipose tissue.The degree of histopathological changes in the groups I-III were similar,but the test group IV was relatively light,indicating that a single gavage of 30 mg/kg bw or 15mg/kg bw praziquantel has a strong systemic toxicity on C.reevesiis.But 3 times by10mg/kg bw,the interval is 3h,it is relatively low toxicity.This study found for the first time that different genders have an effect on the absorption and metabolism of drugs in the C.reevesiis.The peak time of praziquantel in female turtles is about 15h,and the male tortoise is about 74h.For the first time,it is clear that excessive praziquantel can cause strong adverse reactions and systemic tissue toxicity to C.reevesiis.However,it has a certain reversibility,and may recover after autologous repair.The recovery ability of female tortoise is stronger than that of male tortoise.It is recommended that the single intragastric dose of praziquantel used for clinical deworming of turtles is 10 mg/kg b.w or less.If it is necessary to increase the dose,it can be administered multiple times,the female turtle administered continuously within 3 times.