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  • Title: Cefotaxime and desacetylcefotaxime pharmacokinetics in very low birth weight neonates.
    Author: Kearns GL, Jacobs RF, Thomas BR, Darville TL, Trang JM.
    Journal: J Pediatr; 1989 Mar; 114(3):461-7. PubMed ID: 2921690.
    Abstract:
    The single-dose pharmacokinetics of cefotaxime (CTX) and desacetylcefotaxime (dCTX) after a 50.0 mg/kg intravenous dose were evaluated in 18 very low birth weight neonates (13 male; 1015.6 +/- 349.8 gm; 28.4 +/- 2.4 weeks gestational age) during the first week of life. Microanalytic high-performance liquid chromatography was used to quantitate both CTX and dCTX from serum. A two-compartment open model best characterized the disposition of CTX during a 24-hour post-dose period. The disposition of dCTX was adequately characterized by a one-compartment model. The elimination half-life, apparent steady-state volume of distribution, and total body clearance of CTX (mean +/- SEM) were 4.44 hours, 0.461 +/- 0.027 L/kg, and 0.074 +/- 0.003 L/hr/kg, respectively. Peak concentrations (mean +/- SD) of dCTX (17.96 +/- 5.54 mg/L) occurred at 0.6 to 8.3 hours (5.9 +/- 1.9 hours) after CTX administration, and the apparent elimination half-life of dCTX was 9.36 hours. Comparison of CTX and dCTX pharmacokinetic parameters between very low birth weight neonates who weighed less than 1000 gm (n = 9; 703.3 +/- 46.6 gm; 27.0 +/- 0.8 weeks gestational age) and greater than or equal to 1000 gm (n = 9; 1328.8 +/- 48.6 gm; 29.8 +/- 0.5 weeks gestational age) revealed no significant differences, but significant linear correlations were found between gestational age and weight versus CTX half-life and total body clearance. Because of the prolonged clearance of both CTX and dCTX in the very low birth weight neonate, a CTX dose of 50 mg/kg every 24 hours may provide effective serum concentrations for susceptible infections outside the central nervous system.
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