Division C of the acute toxicity of erythromycin
Author: Pan Jing-yuan QIU Yin-Sheng YAN Han-chi
【Key Words】 Division C erythromycylamine
Abstract: Objective: To observe the Division C of erythromycin on acute toxicity in mice and death. Methods: Three different routes of administration in Kunming mice, acute toxicity studies. Results: The intragastric administration of LD50 of 21346 (1761.8 ~ 2586.4) mg / kg, intraperitoneal injection of LD50 dose of 305.5 (272.2 ~
341.9) mg / kg, intravenous administration of LD50 of 121.2 (115.3 ~ 127.3) mg / kg . Conclusion: The Secretary for clinical use of erythromycin C is more secure.
Keywords: Division C erythromycin; mice; acute toxicity
Division C erythromycin (erythormycin propionate | N | acetylcysteinate, EPAC) for the erythromycin derivative, in comparison with erythromycin, which is characterized by high blood concentration after oral administration, long half-life.
This product is mainly caused by susceptible strains of
erythromycin for the treatment of various acute and chronic infection. Safe dose for clinical use of drugs to provide experimental basis for the study of its acute toxicity was studied.
1 Materials and methods
11 subjects materials
Division C erythromycin (EPAC): white powder, the content 980%, batch number 980,907, from hospital rooms to provide synthesis. In Pro, when used with 05% CMC prepared into
various concentrations of suspension.
12 experimental animals
Kunming mice, weighing 19 ~ 21g, male and female in half, provided by the Tongji Medical University. Animals at room temperature for 22 ? 2 ? after the experiment to adapt to
13 test method [1,2]
131 gavage acute toxicity in mice
Mice were 50, fasting 16h were randomly divided into five groups of 10 male and female in half, the ratio of 1:07 between agents, namely, dose, respectively
4200,2940,2058,1440,1008 mg / kg, by 20ml/kg gavage, animals after administration 7d, observe the animals, toxic reactions
and death, with Bliss method LD50.
Intraperitoneal injection of 132 acute toxicity in mice administered
60 mice were taken, fasting after 16h were randomly divided into six groups of 10 male and female in half, the ratio of 1:08 between agents, namely, dose, respectively 5000,4000,3200,2560,2048,1638 mg / kg by intraperitoneal injection 20ml/kg administration, after administration animals 7d, observe the animals, toxic reactions and death situation, experimental results using Bliss method LD50.
Intravenous administration of 133 acute toxicity in mice
Mice were 40, after 16h fasting were randomly divided into four groups of 10 male and female in half, the ratio of 1:09 between agents, namely, dose, respectively 1372,1235,1110,1000 mg / kg, according to 10ml / kg tail vein injection of administration, after administration animals 7d, observe the animals, toxic reactions and death situation, experimental results using Bliss method LD50.
21 intragastric administration acute toxicity in mice
After the mice were gavage 1h autonomous activity started to decrease, apathetic, arched vertical hair, unresponsive to outside stimuli, poor feeding, respiratory depression until death, animal death is generally between 12 ~ 48h after
administration. Autopsy of dead animals, the naked eye no obvious abnormalities in major organs. Survival of animals poisoned to the first 2 ~ 3d later disappeared. Subjects with Bliss method objects lethal dose (LD50) and 95% confidence
limit range. The experimental results shown in Table 1. Table 1 Division C of erythromycin on the LD50 in mice gavage results (omitted) reposted elsewhere in the paper for free download http://
Intraperitoneal injection of 22 acute toxicity in mice
Minutes after intraperitoneal injection of mice with an animal excitement, anger, jumping, the final death spasm. Dead animals, mostly occurs in 48h between the autopsy of dead animals, the naked eye no obvious abnormalities in major
organs. Subjects with Bliss method objects lethal dose (LD50) and 95% confidence limit range. The results in Table 2. Table 2 Division C of erythromycin administration on mice by intraperitoneal injection of the LD50 results (omitted)
23 Intravenous administration of acute toxicity in mice
Tail intravenous injection, the mice immediately appear restless, vertical tail, the final death convulsion. Dead animals, mostly occurs in 12h between the autopsy of dead animals, the naked eye no obvious abnormalities in major
organs. Subjects with Bliss method objects lethal dose (LD50) and 95% confidence limit range. The results in Table 3. Table 3 Division C of intravenous administration of erythromycin on the LD50 in mice results (omitted)
Division C of erythromycin in mice gavage LD50 for 21346mg/kg (1761.8 ~ 2586.4mg/kg); intraperitoneal injection of LD50 dose of 305.5mg/kg (272.9 ~ 341.9mg/kg); intravenous administration of LD50 To 121.2mg/kg (115.3 ~ 127.3mg/kg). [3
EPAC is a synthesis of erythromycin and acetyl-cysteine,
both similar to the antibacterial effect of erythromycin, has a certain mucus dissolution. There is a small water-soluble
erythromycin plasma concentration is low, after oral
administration easily destroyed by stomach acid, gastrointestinal side effects. N-acetylcysteine as a good
phlegm dissolving drugs, a large number of mucus obstruction due to breathing difficulties caused by significant effect, but the use of penicillin, when respiratory inflammation, but also can not use the acetyl-cysteine, because failure to make
penicillin . EPAC is the Red enzymes prime the formation of ester and acetylcysteine salts, acid stability, high serum concentration, half-life long, that is a significant
antibacterial activity, but also has a good mucus dissolution [3 ~ 5]. Therefore, the drug for respiratory infections to provide a new treatment.
The experiment carried out three pairs of EPAC acute toxicity studies showed that, EPAC mice gavage LD50 for
21346mg/kg, the equivalent of the clinical recommended dose per day (37mg/kg) of 58 times; EPAC mice intraperitoneal injection of LD50 dose of 305.5mg/kg, the equivalent of the clinical recommended daily dose of 8 times; EPAC in mice
administered intravenous LD50 for 121.2mg/kg, the equivalent of the clinical recommended daily dose of 3 times. EPAC for clinical oral preparation, indicating EPAC for clinical use is more secure.
The People's Republic of China Ministry of Health
Pharmaceutical Council, a new drug (Western) pre-clinical
study of the guiding principles 1993,143
2 Shu-Yun, Bian Lian, Chen Xiu-pharmacology experiments
Methodology 3rd edition, Beijing: People's Publishing House, 2002,1871 ~ 1885.
3 BernardiM.D, et al. Human pharmacokinetics of erythromycin propionate | N | acetylcysteinate: comparative evaluation with erythromycin stearate and N | acetylcysteine.
Int. J. Clin. Pharmacol. Ther. Toxical. 1988,26 (9): 444
4 Ricevuti G, et al. Serum, Sputum and Bronchial Concentrations of Erythromycin in chronic bronchitis after single and multiple treatments with either Propionate | N | Acetylcsteinate of Stearate Erythromycin. Chemotherapy, 1988,34:374 ~ 379
5 Stubbs. C, et al. Determination of Erythromycin in Serum and Urine by Highperformance Liquid Chromatography with Ultraviolet Detection. Joumal of Pharmaceutical Sciences. 1985,74 (10): 1126 ~ 1128. Reposted elsewhere in the paper for free Download Center http://