249 CHLORAMPHENICOL KINETICS IN INFANTS AND CHILDREN

Abstract

We studied the disposition of chloramphenicol after intravenous administration to 56 infants and children aged one day to 11 years at doses ranging from 12.5 to 100 mg/Kg/day. The mean T 1/2 was 5.94 hrs (range 0.87 - 17.8 hrs); neonates had a longer T 1/2, 8.01 hrs, but not statistically different from non neonates, 5.54 hrs (p = 0.12). The T 1/2 of patients who weighed 10 kg (9.02 vs 4.55 hrs; p < 0.001). In 17 patients the pharmacologic peak concentration (Co) standardized for dose linearly correlated with dosage based on body surface area (r = 0.61) or body weight (r = 0.60). The Co values, however, were highly variable; serum concentrations ranged from 0.39 to 2.43 μg/ml per mg per kg administered (m = 0.97 μg/ml). Eight patients had T 1/2 values which approached infinity; in all eight the concentration of total serum chloramphenicol compounds was greater than biologically active drug during the 8 hour observation period. Four of these 8 patients were hypotensive at the time of the study, but none had laboratory evidence of renal or hepatic failure. One-half of these 8 patients on re-study after clinical improvement had T 1/2 between 4.02 and 20.8 hrs. We conclude that there is a marked individual variation in chloramphenicol pharmacokinetics which is, in part, explicable by delayed hydrolysis of the succinate ester and decreased excretion.