THE EFFECT OF PRAZlQUANTEL ( DRONCIT ) ON CYSTICERCUS PISIFORMIS IN RABBITS

Koudela B., H. Schanzel: The Effect of Praziquantel (Droncit) on Cysticercus pisiformis in Rabbits. Acta vet. Bmo, 47, 1978: 87-90. Rabbits experimentally infested by Cysticercus pisiformis were treated by different single doses of praziquantel (Droncit-Bayer). The drug was administered orally at successive stages of development of cysticerci. The dosage tested of about 8 and 15 mg kg-l and no effect on number, size and vitality of cysticerci. Experimental infection, chemotherapy, oral administration. A new highly efficient cesticidal compound has been developed recently 2-(cyclohexylcarbonyle)-1,3,4,6,7,llb-hexahydro-2H-pyrazino/2,I-a/isoquinolin-4-one, with the following structural formula: The short term for the compound is praziquantel, and the producer, Bayer, delivered it to the market under the name Droncit. The drug is very well tolerated, as has been shown by Miirmann et a1. (1976). In mice and rats, LD5• ranged from 2,000 to 3,030 mg kg-l after oral administration and was even higher when administered parenterally. The LD •• for dogs could not be determined, since doses from 200 mg kg-I resulted in vomiting. Praziquantel showed neither skin-sensibilizing nor embryotoxic and teratogenic effects. Andrews (1976) demonstrated very rapid absorption of praziquantel from duodenum and very rapid distribution to organs CNS included. The drug is rapidly metabolized, probably in the liver, and eliminated. The efficacy of praziquantel on adult tape-worms has been tested mainly in dogs and cats (Giiralp et al. 1976; Rommel et al. 1976; Dey-Hazra 1976). Like with other cesticides, largely different doses were needed depending upon the species of tapeworm involved. Dey-Hazra (1976) achieved complete expulsion of Echinococcus granulosus by a single dose of 5.0 mg kg-l administered to experimentally and naturally infested dogs. A single dose of 2.5 mg kg-l was perfectly effective against Dipylidium caninum, 2.0 mg kg-I against Taenia hydatigena, and, as little as 1.0 mg kg-I against Taenia pisi/ormis in dogs and Taenia taeniaeformis in cats. Referring to the fact that field results are usually a little worse than experimental results, the author recommended an uniform dose of 5.0 mg kg-I. Another matter were the results concerning the effect of praziquantel on larval stages of tapeworms, reported by Thomas et a1. (1975a, b, 1977), Thomas and Andrews (1977 )Lang-

The drug is very well tolerated, as has been shown by Miirmann et a1. (1976).In mice and rats, LD5• ranged from 2,000 to 3,030 mg kg-l after oral administration and was even higher when administered parenterally.The LD •• for dogs could not be determined, since doses from 200 mg kg-I resulted in vomiting.Praziquantel showed neither skin-sensibilizing nor embryotoxic and teratogenic effects.Andrews (1976) demonstrated very rapid absorption of praziquantel from duodenum and very rapid distribution to organs CNS included.The drug is rapidly metabolized, probably in the liver, and eliminated.
The efficacy of praziquantel on adult tape-worms has been tested mainly in dogs and cats (Giiralp et al. 1976;Rommel et al. 1976;Dey-Hazra 1976).Like with other cesticides, largely different doses were needed depending upon the species of tapeworm involved.Dey-Hazra (1976) achieved complete expulsion of Echinococcus granulosus by a single dose of 5.0 mg kg-l administered to experimentally and naturally infested dogs.A single dose of 2.5 mg kg-l was perfectly effective against Dipylidium caninum, 2.0 mg kg-I against Taenia hydatigena, and, as little as 1.0 mg kg-I against Taenia pisi/ormis in dogs and Taenia taeniaeformis in cats.Referring to the fact that field results are usually a little worse than experimental results, the author recommended an uniform dose of 5.0 mg kg-I.
Another matter were the results concerning the effect of praziquantel on larval stages of tapeworms, reported by Thomas et a1. (1975aThomas et a1. ( , b, 1977)), Thomas and Andrews (1977 ) Lang-nes (1976), Horchner et al. (1976), Thomas andGonnert (1976, 1978).Langnes (1976), andHorchner et al. (1976), observed a very good effect on Cysticercus tenuicollis in pigs and a satisfactory result with Cysticercus pisiformis in experimentally infested rabbits after 50 mg kg-1 for 5 days: 60 % of cysticerci were found dead.They started their treatment 8 weeks after infestation, thus at a time when the cysticerci were settled, developed and surrounded by their protective cuticula.Having in mind the importance of the right moment for chemotherapy emphasized by Hinz (1961Hinz ( , 1964) ) particularly for measles of the cysticercus type, we decided to investigate whether even lowered doses of praziquantel would not act efficiently as long as the larvae had not finished migration or the cysticerci missed protection by the outer cuticular layer.

Material and Methods
Rabbits of different breeds, sex (9 males and 18 females) and age (2.5-4.2 kg) were infested by administering a ripe proglottis of Taenia pisoformis orally to each animal.At the day of infestation one animal was treated by half a tablet of Droncit, one by a whole tablet, while a third rabbit remained untreated.At intervals of one week, three more rabbits were treated in the same way.The mean doses of praziquantel were 7.82 ± 0.71 mg kg-1 and 14.86 ± 2.62 mg kg-1 , respectively.Mter 10 weeks of trial, the rabbits were weighed, killed, dissected and examined for number, size and vitality (microthermal test) of cysticerci.Limits of confidence were calculated for statistical evaluation of results.

Results
The results are summarized 10 Table 1: It is obvious that there was no significant difference between the three groups.At no stage of larval development the tapeworm was affected by praziquantel.The cysticerci were equal in size and vitality in both treated and control animals.No side effects were observed.

Discussion
The negative result of our trial is in accordance with the findings reported by Horchner et al. (1976).Though they consider oral administration as less effective than the parenteral way, we do not assume the failure of our treatment was due to the oral way of administration we used.Pharmacokinetical studies performed by Andrews (1976), demonstrated that praziquante1 is equally efficient after oral and parenteral administration.
Neither location and structure of the cysticerci is likely to respond for the failure of treatment.Horchner et al. (1976), who described a very good effect of praziquantel on C. fasciolaris in mice and C. tenuicollis in pigs, met no satisfactory result with C. pisiJormis in rabbits.They concluded that the effect depends rather upon the host species than upon the species of tapeworm.
Compared with our dosage, the doses used by Langnes (1976), andHorchner et al. (1976), were considerably higher.They administered 50 mg kg-1 for 5 consecutive days and even 100 mg kg-1 for 14 days.On the other hand, they treated rabbits not earlier than 8 weeks after infestation, while in our trial praziquantel was administered at different and earlier stages of larval development.Though Thomas and Gonnert (1978), observed in mice that developed larval stages of C. fasciolaris were susceptible to praziquantel while younger stages were not, we feel a new trial would be appropriate, with doses of praziquantel as high and/or repeated as Langnes (1976) and Horchnes et al. (1976) used> but with a timetable and sequence of treatment described in our report.