Chloramphenicol Metabolism

- Aug 28, 2018 -

Chloramphenicol is well absorbed in the gastrointestinal tract and reaches the highest concentration in the blood 1 to 2 hours after oral administration. The drug easily enters the pericardial fluid, pleural fluid, joint cavity fluid, aqueous humor and cerebrospinal fluid in the body. Partial eye drops can make the drug in the aqueous water reach an effective inhibitory concentration, so chloramphenicol is often used as an eye drop. The concentration of the drug in the normal cerebrospinal fluid can reach 40 to 65% of the blood concentration. When the cerebrospinal fluid has inflammation, the concentration can be similar to the blood concentration. Due to the strong lipophilicity of chloramphenicol, the concentration in brain tissue can reach 9 times the concentration of blood. Therefore, chloramphenicol is particularly suitable for the treatment of bacterial meningitis and brain abscess. More than 90% of chloramphenicol enters the human body and combines with glucuronic acid to form metabolites in the liver. This metabolite is non-toxic and has no antibacterial activity. It is mainly secreted and excreted by renal tubules. When the kidney is dysfunctional, this metabolite is in the body. The content will increase, but since it is non-toxic, it is not necessary to reduce the amount of chloramphenicol. The part with antibacterial activity in the body is about 10%. The free chloramphenicol is excreted by glomerular filtration, although its content is not very high, but its concentration still exceeds the required therapeutic concentration of sensitive bacteria, so it can be used for the treatment of urinary, etc. infection. When there is liver dysfunction, the concentration of free drug in the body can be significantly increased, and the possibility of toxic side effects is also significantly increased, so it is necessary to closely monitor the blood drug concentration and reduce the dose in time. The half-life of chloramphenicol is 1 to 4.5 hours (average 3 hours), and the half-life of infants and young children is longer than that of adults. The protein binding rate is about 50-60%. Chloramphenicol esters are incompletely hydrolyzed in the body, and the differences between individuals are also large, and the blood concentration is generally lower than that of chloramphenicol. Chloramphenicol succinate intramuscular injection is not well absorbed, blood concentration? Toxic side effects Mainly have the following categories: 1 blood system. Aplastic anemia is the most serious type, which occurs more than 2 to 8 weeks after administration, and the mortality rate exceeds 50%. It is manifested as irreversible reduction of blood cells, mostly due to bleeding, infection and other factors. There is no fixed relationship between the occurrence and the dose of the drug, and the pathogenesis is still unclear, which may be related to heredity. The other is toxic myelosuppression, clinical manifestations of anemia or accompanied by white blood cells, thrombocytopenia. Its occurrence is closely related to the dosage. When the blood concentration exceeds 25μg/ml, this complication is easy to occur, but it can be recovered after stopping the drug. Its pathogenesis is that the function of mitochondrial synthesis of proteins in bone marrow cells is temporarily inhibited. 2 gray infant syndrome. A systemic circulatory failure caused by high-dose chloramphenicol in premature infants and neonates, showing abdominal distension, vomiting, pale skin, cyanosis, circulatory and respiratory disorders, often dying after a few hours of onset. The pathogenesis is that the binding capacity of hepatic glucuronic acid in premature infants or neonates is insufficient and the ability of glomerular filtration of chloramphenicol is low, so that the concentration of free chloramphenicol in the body is significantly increased, directly inhibiting oxidative phosphorylation of mitochondria in cells. process. 3 digestive system. Often have mild nausea, vomiting, diarrhea, anorexia, etc. 4 nervous system. A small number of patients may have optic neuritis or with peripheral neuritis. Very few patients have headaches, depression, and mental disorders.