Kauffman R E, Miceli J N, Strebel L, Buckley J A, Done A K, Dajani A S
J Pediatr. 1981 Feb;98(2):315-20. doi: 10.1016/s0022-3476(81)80670-1.
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.
在45名年龄从3天至16岁的婴幼儿及儿童静脉注射期间，研究了琥珀氯霉素-3-单酯的代谢及消除情况。氯霉素的表观半衰期变化极大，范围为1.7至12.0小时，平均为5.1小时。表观半衰期与年龄呈负相关。在大多数患者中，氯霉素-S血清浓度呈双指数下降，估计平均初始半衰期为0.7小时，随后较长的平均半衰期为2.2小时。给药后，氯霉素-S在血清中持续存在长达6小时，且在1个月龄以下婴儿血清中占总氯霉素的比例显著高于较大婴儿及儿童。给药的氯霉素-S剂量中，有很大一部分（平均为33%）以原形经尿液排出，因此无活性形式的生物利用度。氯霉素-S的平均肾清除率为259.5 ml/分钟/1.73 M2，是平均肌酐清除率的4倍，表明存在肾小管主动分泌。非水解的氯霉素-S的可变水解及肾消除降低了抗生素的生物利用度，似乎是导致表观半衰期广泛变化以及游离氯霉素剂量与血清浓度之间相关性差的主要原因。
