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Chloramphenicol succinate kinetics in infants and young children
C M Sack1, J R Koup, K E Opheim
1Department of Pediatrics, University of Washington, Division of Infectious Disease, Children's Orthopedic Hospital and Medical Center, Seattle 98105, USA.
Insights
Urinary excretion of chloramphenicol succinate (CmS) impacts its bioavailability and subsequent chloramphenicol (Cm) levels in children. However, CmS half-life variations minimally affect Cm half-life, suggesting prodrug excretion is key.
Area of Science:
- Pharmacology
- Pediatric Pharmacokinetics
- Drug Metabolism
Background:
- Chloramphenicol succinate (CmS) is a prodrug used for intravenous administration of chloramphenicol (Cm).
- Understanding the pharmacokinetics of CmS and its influence on Cm is crucial for optimizing pediatric dosing regimens.
Purpose of the Study:
- To determine the serum and urine pharmacokinetics of CmS in pediatric patients.
- To evaluate how variations in CmS pharmacokinetic parameters affect the kinetics of the active drug, Cm.
Main Methods:
- Serum and urine samples were analyzed from 24 infants and young children (2 weeks to 7 years).
- Pharmacokinetic parameters including half-life (T(1/2)), body clearance, and volume of distribution were estimated for CmS.
- Urinary excretion of CmS was quantified over the dosing interval.
Main Results:
- The mean T(1/2) of CmS was 0.40 hours, with a mean body clearance of 0.72 L/kg/hr and a mean apparent volume of distribution of 0.42 L/kg.
- Urinary excretion accounted for a mean of 35% of the administered CmS dose.
- No significant correlation was found between CmS T(1/2) and Cm T(1/2) (r² = 0.002, P = 0.84).
- Infusion duration did not alter urinary CmS loss.
Conclusions:
- Variations in urinary CmS excretion significantly influence the bioavailability of Cm.
- The amount of CmS excreted in urine impacts secondary pharmacokinetic parameters like volume of distribution and body clearance of Cm.
- While urinary prodrug excretion is a critical factor, variations in CmS T(1/2) have minimal impact on Cm T(1/2).
Abstract:
We sought to estimate the serum and urine pharmacokinetics of chloramphenicol succinate (CmS) and the effects of variation of these parameters on chloramphenicol (Cm) kinetics in 24 infants and young children ages two weeks to seven years. The mean T(1/2) of CmS was 0.40 hours; the mean body clearance was 0.72 liter/KG/hour; the mean apparent volume of distribution was 0.42 liter/kg. Variation in CmS T(1/2) did not correlate with significant variation in Cm T(1/2) (r2 = 0.002, P = 0.84). Urine collected during the dosing interval in nine patients contained 35% (mean) of the administered dose. Adjusting the infusion duration to 5 minutes or 120 minutes had no effect on the amount of CmS lost in the urine. The quantity of CmS lost in the urine affects the amount bioavailable, and secondarily the calculated volume of distribution and body clearance of Cm. We conclude that variation in urinary prodrug excretion affects the amount of Cm bioavailable to the patient, but variation in CmS T(1/2) has little effect on Cm T(1/2).