Study On Treatment Of Schistosomiasis Japanum With Praziquantel Via Skin

In order to evaluate the effect of Praziquantel（PZQ） administration via skin on the treatment of Schistosomiasis japanum,The solubilities of PZQ in five different solvents,namely,ethylene glycol monophenyl ether（EGPE）,1,4-dioxane, tetrahydrofuran（THF）,dimethyl sulfoxide（DMSO）,oleic acid（OA）,were measured. The results showed the solubility of PZQ in EGPE was much higher than the others’, maintained above 400 mg·mL^-1.And it reached at 490 mg·mL^-1 at 37℃,which was 4.9 times as PZQ concentration in transdermal agents reported.The solubility of PZQ in 1,4-dioxane maintained at 220～284 mg/mL in the temperature range from 25 to 35℃.It kept above 440 mg/mL above 37℃,were 4.4 times as PZQ concentration in transdermal agents reported.And the solubility of PZQ in DMSO,OA and THF maintained at a relative low level,about 100 mg·mL^-1.The n-octanol/water partition coefficient of PZQ in the five solution mention above were determined,the results showed LogP value of EGPE and OA solution were 0.895,0.653,higher than-0.167 of DMSO,0.182 of 1,4-dioxane,0.0378 of THF.The result of study on Pharmacokinetics property showed the blood drug peak concentration(C_max) were reached at 30 min after transdermal administration of PZQ solutions.The C_max of EGPE solution is highest with a concentration of 18.36μg/mL,followed by that of DMSO with a concentration of 11.74μg/mL.And the C_max of 1,4-dioxane solution, OA solution and THF solution were 1.58,3.02 and 3.47μg/mL respectively.When the PZQ EGPE solution was used for transdermal administration,the serum drug blood concentration maintained 4.0μg/mL over 4 h is sufficient for the treatment of schistosomiasis.The relative bioavailability of EGPE,DMSO,OA,THF and 1, 4-dioxane solution via skin to PZQ tablets via oral were 2.85,1.89,1.68,0.67,and 0.54 respectively.The mixed solvents system were studied,and the results showed the solubility of PZQ with a concentration of 429 mg·mL^-1 were highest when the volume content of ethanol was 50%.When PZQ EGPE solution was used for treatment of Schistosomiasis japanum in mice,100%of worm-reduction rate and 93.5%of the egg-reduction rate were obtained.And 100%of worm-reduction rate and 95.0%of the egg-reduction rate were obtained when it was used for treatment of Schistosomiasis japanum in rabbits.The observation to liver tissue section showed that the diameter and the area of hepatic granuloma from treated group were much smaller than that of blank group.The fact showed that PZQ had not only sufficient killing effect on Schistosomiasis japanum body but also notable inhibitory effect on hepatic granuloma.