desacetylcefotaxime and Hemolysis

The metabolism of cefotaxime (CTX) by hemolyzed blood at different concentrations, time intervals, and temperatures was studied. Cefotaxime and desacetylcefotaxime (DES) levels were quantitated by reverse phase high pressure liquid chromatography. When CTX was added to tubes with 10% hemolysis, CTX/DES levels (micrograms per milliliter) were 123/134, 161/114, and 202/60 at 37 degrees C, room temperature, and 4 degrees C, respectively, after a 1 hr incubation. No reduction in CTX was observed in control experiments (10% blood, no hemolysis) at these temperatures after 1 hr; 200 +/- 23 micrograms/ml CTX; 5 +/- 2 micrograms/ml DES. The disappearance half-life of CTX in 10% hemolyzed blood at 37 degrees C was 45.7 min and at room temperature 84.3 min (p less than 0.001). The addition of the enzyme inhibitors ethylenediaminetetraacetic acid and p-hydroxymercuibenzoate reduced the metabolism of CTX in the presence of 10% hemolysis after 1 hr at 37 degrees C from 41% to 19% with ethylenediaminetetraacetic acid (0.45 mM) and to 0% with p-hydroxymercuibenzoate (10 mM). Our results suggest that for accurate determinations of CTX serum levels, which often have some degree of hemolysis, such specimens should be collected in tubes with ethylenediaminetetraacetic acid or p-hydroxymercuibenzoate and transported at 4 degrees C.

Topics: Adult; Cefotaxime; Chromatography, High Pressure Liquid; Edetic Acid; Half-Life; Hemolysis; Humans; Hydroxymercuribenzoates; Temperature; Time Factors

Cefotaxime was given to neonates as treatment of infection in a dose of 25 mg/kg 12 hourly by intravenous injection. Blood samples taken by heel-prick were specially treated to minimize any effect of haemolysis on the hydrolysis of cefotaxime. The mean peak plasma concentrations of cefotaxime on the first, second and third days of therapy were 43, 40 and 52 mg/l, respectively, with mean plasma half lives of 4.0, 2.7 and 3.2 h. The mean peak concentrations of desacetyl-cefotaxime were about a quarter of those of cefotaxime, which is in good agreement with adult studies, but much lower than those previously published in studies with neonates. These results emphasize the care that is necessary in the assay of body fluids and tissues for cefotaxime and desacetyl-cefotaxime if accurate results are to be obtained.

Topics: Cefotaxime; Half-Life; Hemolysis; Humans; Infant, Newborn; Kinetics