Pharmacokinetics of chloramphenicol and chloramphenicol succinate in infants and children.
The metabolism and elimination of chloramphenicol-3-monosuccinate was studied in 45 infants and children, ages 3 days to 16 years, during intravenous administration. The apparent half-life of chloramphenicol was extremely variable, ranging from 1.7 to 12.0 hours with a mean of 5.1 hours. Apparent half-lives were inversely correlated with age. Chloramphenicol-S serum concentration declined biexponentially in most patients, with an estimated mean initial half-life of 0.7 hours and a subsequent longer mean half-life of 2.2 hours. Chloramphenicol-S persisted in serum up to six hours after a dose, and comprised a significantly larger fraction of total chloramphenicol in the serum of infants under one month of age than in older infants and children. A widely variable fraction of the administered chloramphenicol-S dose, with a mean of 33%, was excreted in the urine unchanged and was, therefore, not bioavailable in active form. Mean renal clearance of chloramphenicol-S was 259.5 ml/minute/1.73 M2, four times the mean creatinine clearance, indicating active tubular secretion. Variable hydrolysis and renal elimination of nonhydrolyzed chloramphenicol-S reduces the bioavailability of the antibiotic and appears to contribute substantially to the wide variation in apparent half-life and poor correlation between dose and serum concentration of free chloramphenicol.
D000293:Adolescent; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D002701:Chloramphenicol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D003404:Creatinine / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008657:Metabolic Clearance Rate
D002701:Chloramphenicol; D003404:Creatinine; C026016:chloramphenicol succinate