| ObjectiveIn order to observe the efficacy of tribendimidine (TBD) oral administration at different dosages against Trichinella spirails encapsulated larvae in striated muscle in mice. To compare the curative effect of tribendimidine (TBD) oral administration at different courses of treatment against encapsulated larvae of Trichinella spirails in striated muscle in mice. To observe the efficacy of three different oral liquid formulations of tribendimidine (TBD) against Trichinella spiralis encapsulated larvae in mice.Materials and MethodsExperiment1:A total of88BALB/c mice were divided equally into11groups orally infected each mouse with50encapsulated larvae. TBD was each orally administered to mice with doses of0-500mg/(kg-d), respectively on day29after infection. All of mice were administered once a day and lasted for6d, and the drug untoward reactions for mice were observed. On the day7after administration, the larvae in diaphragmatic, jugomaxillary. pectoral and gastrocnemius muscle were observed with pellet method. The therapeutic effect was estimated on the basis of average quantity of larvae in per gram muscle.Experiment2:Forty mice were randomly divided equally into5groups, each mouse infected orally with50encapsulated larvae. TBD was administered each orally to5groups with300mg/(kg-d) at different courses of treatment (lasted for2,4,6or8d). respectively on day29after infection, control group was not treatment. Then the drug untoward reactions for mice were observed. On the day7after drug withdrawal, the larvae in diaphragmatic, jugomaxillary, pectoral and gastrocnemius muscle were counted with pellet method. Another40mice were randomly divided equally into5groups, each mouse infected orally with50encapsulated larvae in diaphragmatic muscle of mice that orally administered TBD300mg/(kg-d) at different courses of treatment. On the day29after infection, larvae in diaphragmatic muscle were counted with pellet method.Experiment3:Forty mice were divided equally into4groups in which each mouse infected orally with50encapsulated larvae. On day29post infection, TBD was administered orally via gastric tube to three treatment groups with200mg/(kg-d) at three different oral liquid formulations and lasted for6d respectively, and control group was not treated. For Tween group. TBD were dissolved in7%Tween-80and3%ethanol; for CMC group, TBD were dissolved in1%CMC and3%ethanol; for HP-β-CD group, TBD were dissolved in7%HP-β-CD and3%ethanol. Mice were sacrificed on the14d post-treatment. The larvae in diaphragmatic and gastrocnemius muscle were observed with pellet method and the total, survival and dead worms were counted. The therapeutic effect was estimated on the basis of average quantity of larvae in per gram muscle.ResultsExperiment1:The untoward reaction were not for mice in50-300mg groups; severe untoward reaction were found for mice in350-400mg groups, death rates were25%and50%. respectively; all mice in450and500mg groups were died. TBD50mg cannot effect to worm burden in muscle, the total worm burden and survival worms were downtrend and dead worms were raise tendency in four muscles as the dosage of TBD increased. Compare with control, the total and survival worms in4muscles were significantly decreased, among of these the survival worms in300mg group were significantly lower than that of control (P<0.01), all mice in350and400mg groups in the above muscles were death (P<0.01).Experiment2:The drug adverse reaction for mice was not detected. The total worm burden and survival worms were downtrend and dead worms were raise tendency in four muscles as the course of treatment increased. Compared with the control group, the total and survival worms in diaphragmatic, jugomaxillary and gastrocnemius muscle of2d and over2d courses of treatment were significantly decreased (P<0.05, P<0.01), the total worm in pectoral muscle of6d and8d courses of treatment groups were significantly decreased (,P<0.05. P<0.01). As the courses of treatment increasing, the death rate of encapsulated larvae were raise tendency in four muscles, and that in6d and8d courses of treatment group were96.16%-99.13%and99.62%-100%respectively (P<0.01). The authenticity infection for curative effect indicated that infection rates in6d (37.5%) and8d courses of treatment groups (12.5%) were significantly lower than that of in control group (100%) and2d courses (100%)(P<0.01).Experiment3:Untoward reaction was not found for all mice. Compared with the control, the total and survival worms in diaphragmatic and gastrocnemius muscle in three treatment groups were significantly decreased (P<0.05or P<0.01), and the dead worms were significantly increased (P<0.01). The efficacy in HP-β-CD group was the highest in three treatment groups. The total worm reductions were evaluated, the relative bioavailability of TBD in CMC and HP-β-CD groups (diaphragmatic muscle:1.61and2.13-fold; gastrocnemius muscle:2.46and2.49-fold) in mice were significantly increased in comparison with Tween group. The death worms were evaluated, and these data were1.55and2.51-fold in diaphragmatic muscle and2.51and2.16-fold in gastrocnemius muscle.ConclusionThese results shown that oral administered TBD50mg/(kg·d) to mice for6d did not effect to worm burden in muscle. TBD300mg/(kg-d) could effectively kill encapsulated larvae and was a suitable dose against encapsulated larva stage of the parasite. However. TBD350mg/(kg-d) or larger doses for6d showed toxic action to mice and even causing death.Oral administered TBD300mg/(kg-d) to mice for6day or8day could not detect adverse drug reaction, and could effectively kill encapsulated larvae and was a suitable course of treatment against encapsulated larva stage of the parasite.These results shown significantly increased bioavailability of TBD and efficacy against Trichinella spiralis encapsulated larvae in mice for the formulation of TBD dissolved in7%HP-p-CD and3%ethanol or1%CMC and3%ethanol, the efficacy of7%HP-p-CD and3%ethanol was the best. |
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