Abstract
CS must be hydrolyzed to C to provide antimicrobial activity. A thorough knowledge of CS disposition is needed to understand C kinetics in children. Thirty patients (age 1.5 wk-17 yr) were studied to characterize CS and C kinetics. CS, 25 mg/kg was administered every 6 hr intravenously over 0.5 hr. At steady state, blood samples were obtained at 0, 0.5, 1, 2, 4 and 6 hr after starting the infusion. In 10 patients, all urine was collected over the same 6 hr. CS and C concentrations (cone) were measured by an HPLC method. Peak serum CS cone ranged from 7.38-79.5 mcg/m1 and peak C cone from 9.3-66.21 mcg/m1. A rapid decline in serum CS cone was followed by a slow elimination phase in half of the patients. CS was still detectable in serum at 4 hr in 10 patients and 6 hr in 9 patients. Disposition of both CS and C appeared to be a first order process. Half-life of CS ranged from 0.3-5.5 hr and of C from 1.6-7.9 hr. Total body clearance of CS ranged from 0.152-3.27 L/kg/hr and of C from 0.043-0.425 L/kg/hr. 5-25% of the total dose of CS was excreted in the urine as either C (2-7%) or CS (3-18%). These data suggest that CS kinetics may be characterized by a two compartment open model. Its hydrolysis is not instantaneous but more variable than previously appreciated. These factors may account for the large variability in C kinetics found in our study and described in previous reports of C pharma-cokinetics in children.
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Nahata, M., Powell, D., Glazer, J. et al. 350 KINETICS OF CHLORAMPHENICOL (C) AND ITS SUCCINATE ESTER (CS) IN PEDIATRIC PATIENTS. Pediatr Res 15 (Suppl 4), 498 (1981). https://doi.org/10.1203/00006450-198104001-00361
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DOI: https://doi.org/10.1203/00006450-198104001-00361