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KMID : 0351619750160020119
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Kyungpook Medical Journal
1975 Volume.16 No. 2 p.119 ~ p.130
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Toxicological studies of a Chemotherapeutic Compund Nichlozol
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Abstract
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In spite of milIians of people having suffered from Clonorchiasis sinensis, an effective drug had not been found until last decade. Fcrtunalely, in recent years many drugs such as MTPA, Hetol and Niclofolan were introduced and the effectivenese was proved clinically. B:~t these were also proved to have toxicity and many side effects. As yet drub;s `vhich have less toxic and more effective or ne~v methods of the drug therapy lessning clinical toxicity are desirable. For the latter purpose futher toxicological studies of above mentioned drug;s are necessary.
The present paper deals with toxicologic propertis of Nichhlozol, anew compound, Niclofolan and MTPA. The toxicity studies were performed in rabbit of b~~th sex weighing 2.0~-2.5kg.
In acute studies Nichlozol 200mg/kg, Niclofolan 20mg/kg, lOmg/kg, b2TPA 30m6~`kg, 50mg/kg icily for 3--6days and in subacute studies Nichlozol 80mg/kg, 40:ng/kg, Niclofolan 8mg/kg, 4mg/kg,MTPA 35mg/kg, daily for 15 days were administered orally in each rabbit respectively. A groups was composed of 5 rabbits according to the dosage of each drug. The rabbits were observed ´on behavior and appearance daily during treatment, prior and. after treatment bodv weight hematol grcal and serum bixhemical studies were performed. After treatment the histological finding of the kidney and liver were obserbed.
The following results were obtaind.
1. In"rabbits receiving Nichlozol at a doss of 200mg/kg/day for 4 days, during experiment death if a rabbit occured, and remainder shy:ved decreasa in red gall, white cell, h:no3obin and heratoxit, and also rise of GOT in on rabbit. No alteration was observed in total protein and protein
2. In rabbits being given Nichlozol at a does cf 80mg/kg/day for 15 days, durin; esp~riment death of 2 rabbits cccured and the remainder showed a decrease of white cell, hemcgl~bia and total protein. No considerable changes were observe3 in protein pattern, alkaline phosphatas~, GOT and GPT
3. In group receiving Niclofolan at a dose of 20mg/kg/day for 3 days rabbits ~;ec~n:e excited at second clay and depressed at third day and one of tl~e rabbit was expired. Tiie rem zaindes showed ´a decrease of red cell, white cell, hemoglobin and hematocrit. Arise of GOT ir: 3, GPT in one and alkaline phesphatase slight in all rabbits vrere noted.
4. In rabbits receiving Niclofolan lOmg/kg/day for 6 days rio behavior change were noted during treatment. After treatment no alteration in total protein, protein pattern and GPT level but rise GOT in one, and slight decrease in red cell and white cell in all rabbits were found
5. In rabbits receiving Niclofolan at dose of 8mg/kg/day for 15 days, 2 rabbits were expired in 3th day and 12th day of experiment. The remaind showed a slight decrease in red. cell~and White -h~´ ._, ~* Il, ~ hemoglobin and total protein in all but rise in GOT in 2 rabbits.
6. In rabbits receiving MTPA at a dese of 80m3~/kg/day fer 6 days, 2 of them disclosed a de ease of appetite, a slight depression, but in 3 the normal behavior. After treatment, a slight de ease in red cell, white cell and hemoglobin, a rist;,in GOT in one, GPT in 2 rabbits were obserbd
7. In rabbits receiving MTPA at a dose cf 50mg/kg/day for 6 days no behavior change wer seen. After administration of drug blood finding remaind normal but GPT level were elevated in rabbits
8. In groups of \ichlezol 40mg/kg, Niclofelan 4mg/kg, MTPA 35mg/kg for 15 days respectively ´ normal bel~avcir, appetite and weight gain were noted and after administration of drug blood finding and liver furctien remained normal
9. In all groups, urine, histological finding of liver an?sidney demonstrated no change eYCept: a MTPA 80mg/l:g group in which a slight inflarsmal;ory c´~ange were noted in the liver.
From the above experimental result it may conclude that in dose exceeding 4 tir:~es cf effective dose of those drugs ir. mer. the rabbits exhibit toxicity but in dose cf 3~-2 times cf effective dose´ in men even the rabbits with continued adr.~inistration of these drug fer 15 day were well talelated.
It seems safe in man with therapeutic dose but the efective dese and response to the drug vaies: considerably bet:veen human and animal a :d therefor tu:ther tolicity studies in men rr_: y be nece ssary.
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