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Pharmacokinetics of chloramphenicol and chloramphenicol succinate in infants and children

1981; Elsevier BV; Volume: 98; Issue: 2 Linguagem: Inglês

10.1016/s0022-3476(81)80670-1

1097-6833

Ralph E. Kauffman, Joseph N. Miceli, Leon Strebel, Joyce A. Buckley, Alan K. Done, Adnan S. Dajani,

Drug Transport and Resistance Mechanisms

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.