Elimination Kinetics of Cefotaxime and Desacetyl Cefotaxime in Patients with Renal Insufficiency and during Hemodialysis

Abstract

The pharmacokinetics of cefotaxime, a new semi-synthetic cephalosporin for injection, was studied in 30 subjects with various degrees of renal function after a single 1-gram intramuscular injection. Serum and urinary concentrations of cefotaxime and desacetyl cefotaxime were determined by high pressure liquid chromatography. The pharmacokinetic parameters of cefotaxime were obtained using a one-compartment open model. The mean serum half-life of the parent compound (cefotaxime), 0.87 h in normal subjects, was prolonged to 2.35 h in hemodialysis patients. There was a significant lineal correlation between the elimination rate constant of cefotaxime and creatinine clearance. The mean cumulative urinary recovery of the administered dose in the 24-hour urine was 51.7% as cefotaxime and 25 6% as desacetyl cefotaxime in normal subjects.

Cefotaxime and desacetylcefotaxime pharmacokinetics in infants and children with meningitis

“…In our subjects, the urinary excretion of unchanged Ctx during the 6-h postinfusion period (approximately 61%) was in close agreement with values reported for adults with normal renal function (5,12,14). The CLR of Ctx in our subjects (0.174 liter/h per kg) was similar to that in adults with normal renal function (165 ml/min per 1.73 m2 or approximately 0.141 liter/h per kg) (29). The mean CL of Ctx in our subjects (0.289 liter/h per kg) was in close agreement with values reported for adults with normal renal function (approximately 0.234 to 0.307 liter/h per kg) after Ctx quantitation by HPLC (16,29).…”

“…The CLR of Ctx in our subjects (0.174 liter/h per kg) was similar to that in adults with normal renal function (165 ml/min per 1.73 m2 or approximately 0.141 liter/h per kg) (29). The mean CL of Ctx in our subjects (0.289 liter/h per kg) was in close agreement with values reported for adults with normal renal function (approximately 0.234 to 0.307 liter/h per kg) after Ctx quantitation by HPLC (16,29). The differences between CL of Ctx in our patients and that in full-term, newborn infants (2,26) were consistent with expected developmental differences in renal function and body mass-water relationships between the two age groups.…”

“…236,1984). The disposition of Ctx and dCtx in serum has also been evaluated in adults with normal and impaired renal function (16,29,37). Few studies, however, have characterized the serum and CSF disposition of both Ctx and dCtx in infants and children with meningitis during a therapeutic course of Ctx (15).…”

Pharmacokinetics of cefotaxime and its active metabolite in children with renal dysfunction

“…Cefotaxime is unique among the expanded-spectrum cephalosporins in that it is partially metabolized to desacetylcefotaxime, which retains 1/2 to 1/10th of the parent compound's antimicrobial activity (3,5). Both cefotaxime and desacetylcefotaxime pharmacokinetics were affected by renal dysfunction in adults (4,6,7). Approximately 40 to 60% of cefotaxime was excreted renally in adults with normal renal function (4,6,7).…”

“…Both cefotaxime and desacetylcefotaxime pharmacokinetics were affected by renal dysfunction in adults (4,6,7). Approximately 40 to 60% of cefotaxime was excreted renally in adults with normal renal function (4,6,7). It has also been reported that the elimination half-life (t4/2) of the desacetyl metabolite was extended during renal dysfunction in adults (4,6,7).…”