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4.
1.
2.
1 Metabolic processes in the body
(1)CAP
Most CAP is inactivated by combining with glucuronic acid in the liver, and a small part is degraded into aromatic amines
.
About 10% of the original CAP is excreted by the kidneys and can also be secreted through milk
(2) TAP
The pharmacokinetic studies of TAP in sheep and dairy cows have also been reported
.
The drug was administered to sheep through three ways: intravenous injection, intramuscular injection, and oral administration.
(3)FF
FF is rapidly absorbed, widely distributed, and highly bioavailable in animals, and its pharmacokinetics in aquatic animals, chickens, sheep, pigs and other animal tissues have been reported
.
Three hours after oral administration of fish (dose of 10mg/kg), there are high concentrations of FF in all tissues and organs.
Feeding Atlantic salmon with 14 C-labeled FF, it was found that FF and its metabolites have higher binding power with melanin.
The main metabolite of FF in fish muscle tissue is FFa
.
The 10 mg/kg body weight single-dose intravenous injection, oral and multi-dose feeding tests were performed on Atlantic salmon, and the results were quantified by high performance liquid chromatography.
36 healthy broilers were injected intravenously and intramuscularly at two doses of 15 mg/kg and 30 mg/kg respectively.
The drug concentration in plasma was determined by high performance liquid chromatography, and the drug-time data was processed by 3P97 pharmacokinetic program software.
.
The intravenous injection-hour data accords with the two-compartment opening model, and the intramuscular injection-hour data accords with the one-compartment opening model.
The pharmacokinetic test results of intravenous and intramuscular injection of FF in sheep show that the area under the curve AUC is proportional to the dose after intramuscular injection of FF, which is well absorbed in sheep, quickly distributed, and slow in elimination
.
The in vivo pharmacokinetics test of FF was carried out on healthy pigs and pigs infected with Actinobacillus pleuropneumoniae.
18 pigs infected with Actinobacillus pleuropneumoniae were used as experimental animals.
Three routes of intramuscular injection and oral administration were used.
The concentration of FF in plasma was determined by high performance liquid chromatography.
The pharmacokinetic parameters were processed by the MCPKP software program
.
The highest plasma concentration after intramuscular injection and oral administration were 4.
FF's metabolism test shows that it is mainly metabolized into extractable residual substances in salmon; it is mainly metabolized into non-extractable residual substances in pig, poultry, and cattle tissues, but these substances are hydrolyzed into metabolites that can be quantitatively extracted— FFa
.
The analysis of FFa can more accurately quantify the related total metabolites of FF in the tissue
4.
1.
2.
2 Toxicology and adverse reactions
CAPs have a broad antibacterial spectrum and strong antibacterial effects, but their side effects cannot be ignored
.
CAP mainly inhibits human hematopoietic function, TAP mainly inhibits human immune function, with greater toxicity; while the new chloramphenicol antibiotic FF has less toxic effect and is mainly toxic to animal embryos
CAP has serious toxic effects on the human hematopoietic system and digestive system, and can also cause adverse reactions such as optic neuritis and skin rashes
.
CAP is extremely toxic to the human hematopoietic system.
It can reduce white blood cells, cause aplastic and hemolytic anemia and thrombocytopenia; it can also damage vision, cause acute toxic epidermal relaxation, and cause eyelid adhesion and corneal scarring.
.
CAP has a greater impact on newborns, premature infants, patients with liver and kidney dysfunction, and the elderly
.
In recent years, there have been reports of deaths caused by overdose of CAP in children and use of CAP ophthalmic ointment by elderly women
.
Therefore, CAP has been discontinued in human medicine in the 1980s and 1990s; in veterinary clinics, many countries including China have banned the use of CAP in food animals
.
TAP also has hematological toxicity, mainly manifested as reversible erythropoiesis inhibition, but no reports of aplastic anemia have been reported
.
TAP has a strong immunosuppressive effect, which is about 6 times stronger than CAP.
It should be banned for animals during vaccination or animals with severely impaired immune function
.
Both the European Community and the United States are banned from food animals .
In the FF structure, —CH 3 SO 2 is used to replace —NO 2 on CAP, which is related to the inhibition of bone marrow hematopoietic function , which greatly reduces the toxicity to animals and humans, and there is no potential risk of aplastic anemia
.
Moreover, studies have shown that FF has no teratogenic, carcinogenic and mutagenic effects
.
FF will not cause chromosome structural or quantitative aberrations; under the condition of S9 activation system, it will not cause mutations in the TK site in mouse lymphoma L5178Y cells, and will not induce mutations under acute or subacute administration conditions.
Chromosomal aberrations in bone marrow cells have not been found to have mutagenic effects by examining micronuclei
.
However, the reproduction toxicity test showed that FF has embryo toxicity, which significantly reduces the weight of the epididymis of F1 male rats, and the lactation index of F2 pups is reduced, and the survival rate is also reduced.
Therefore, it is recommended to breed cattle and pregnant and lactating cattle ( Including cows) banned
.