Objectives: In this study, the acute toxicity of pidotimod synthesized in Vietnam have been evaluated. Materials are synthetic pidotimod offered by Hanoi University of Pharmacy. Equipments and chemicals used for the study was calibrated according to ISO/IEC 17025.
The test groups were given a test suspension at the dose and dose levels shown in table Table 1: Volume and dosage of test sample used in mice Dose Dosage Dosage Number of mice level (mL sample/20 g mouse) (g sample/kg mouse) ML 0.6 mL 15.0 g/kg 10 ML 0.7 mL 17.5 g/kg 10 ML 0.8 mL 20.0 g/kg 10 ML 0.9 mL 22.5 g/kg 10 ML 1.0 mL 25.0 g/kg 10 ML 1.1 mL 27.5 g/kg 10 - Tracking calendar: Track expression of mouse activity after drinking, 24 hours and days 92 Journal of military pharmaco-medicine n09-2018 RESULTS The results of the probe not killing mice After 24 hours, the mice which received a test suspension of 10.0, 12.5 and 15.0 g/kg were not killed, while at the dose of 17.5 g/kg one mouse was killed So no lethal dose should not exceed 15.0 g/kg Results of probe dose at 100% killing mice study After a 24-hour follow-up, the mice at the dose of 25.0 g/kg killed four fifth of the group mice, while at 27.5, 30.0 and 32.5 g/kg doses, 100% of the mice killed So the lethal dose of 100% of the mice Results of monitoring feed and oral consumption of mice After oral ingestion at ML1 dose level, mice showed normal activity At the ML2, ML3, ML4, ML5 and ML6 doses, after administration of test, mice exhibited decreased physical activity Mice that did not die at the above dose levels reduced feed intake during the follow-up period Results of observation signs of poisoning At the ML2, ML3, ML4, ML5 and ML6 doses, after administration of test suspension, mice demonstrated exhibited decreased activity and fatigue Mice died for a period of to 24 hours Mice that did not die at the above dose levels showed decreased activity, fatigue during follow-up than Mice at ML1 dose did not find evidence of toxicity Thus, the LD50 was determined in the range of 15.0 to 27.5 g/kg Monitoring the mortality/alive mice ratio when given a test at the dose levels was shown in table and figure should therefore be no less 27.5 g/kg of sample mice Table 2: Results of monitoring dead and alive mice Dose Dosage level (g sample/kg mouse) Number of dead/alive mice Dead/alive mice % death ML 15.0 0/10 0/33 ML 17.5 1/9 1/23 4.17 ML 20.0 3/7 4/14 22.22 ML 22.5 5/5 9/7 56.25 ML 25.0 8/2 17/2 89.5 ML 27.5 10/0 27/0 100 93 Journal of military pharmaco-medicine n09-2018 Figure 1: Chart of correlation of dose and proportion dead mouse Calculating the LD50 by Behrens formula lead to the value of 22.041 ± 0.649 g/kg After administration of the drug, mice exhibited the following symptoms: At low doses (15.0 g/kg of mice), there was no evidence of toxicity; at doses from 17.5 to 27.5 g/kg, mice exhibited fatigue, decreased activity Mice died in the to 24 hours and the death rate was dependent on the oral dose In this trial, the non-killing dose found was 15.0 g/kg samples mice The killing dose of 100% of the test mice was 27.5 g/kg samples mice Based on actual data, we found the dose of LD50 = 22.041 ± 0.649 g/kg The substances whose LD50-grade toxicity are greater than 5,000 mg/kg mice administered orally are considered to be non-toxic CONCLUSION The acute toxicity level of the synthesized pidotimod sample was studied 94 The results showed that the LD50 value was 22.041 ± 0.649 g/kg Thus, based on the results of this test, it can be concluded that pidotimod sample (P120513) belongs to the class of non-toxic substances REFERENCES Do Trung Dam Methods of toxicity determination of drugs Medical Publishing House 2014, pp.101-112 Vietnam Ministry of Health Circular 03/2012/TT-BYT Guidelines for Clinical Trials on Drugs 2012 K Adams et al Genotoxicity testing of pidotimod in vitro and in vivo ArzneimittelForschung 1994, 44 (12A), pp.1454-1459 Globally Harmonized System of Classification and Labelling of Chemicals 2017 Magni A., Signorelli G., Bocchiola G Arzeim-Forsch/Drug Res Synthesis and preliminary pharmacological evalution of pidotimod, its enantiomers, diastereomers and carboxamido derivatives 1994, 44 (II), 12A, pp.1402-1404 ... of non-toxic substances REFERENCES Do Trung Dam Methods of toxicity determination of drugs Medical Publishing House 2014, pp.101-112 Vietnam Ministry of Health Circular 03/2012/TT-BYT Guidelines... decreased activity, fatigue during follow-up than Mice at ML1 dose did not find evidence of toxicity Thus, the LD50 was determined in the range of 15.0 to 27.5 g/kg Monitoring the mortality/alive mice... of the group mice, while at 27.5, 30.0 and 32.5 g/kg doses, 100% of the mice killed So the lethal dose of 100% of the mice Results of monitoring feed and oral consumption of mice After oral ingestion