Cefotaxime and desacetyl cefotaxime kinetics in renal impairment

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Abstract
Cefotaxime and desacetyl cefotaxime kinetics after a single, 1 g i.v. dose were evaluated in 5 groups of subjects: group I, normal creatinine, clearance (CLCR > 90 ml/min); group II, mild renal insufficiency (CLCR 30-89 ml/min); group III, moderate renal insufficiency (CLCR 16-29 ml/min); group IV, severe renal insufficiency (CLCR 4-15 ml/min); and group V, end-stage renal disease requiring maintenance hemodialysis (CLCR < 6 ml/min). The steady-state volume of distribution (Vss) ranged from 10%-55% of body weight but was not related to CLCR. The terminal t1/2 [half-time] values of cefotaxime and desacetyl cefotaxime were 0.79 and 0.70, 1.09 and 3.95, 1.55 and 5.65, 2.54 and 14.23, and 1.63 and 23.15 h in groups I to V, respectively. There were no significant changes in Vss or t1/2 after multiple dosing, but there were significant correlations between CLCR and cefotaxime total body clearance, cefotaxime and desacetyl cefotaxime renal clearance, and cefotaxime nonrenal clearance. Dosage regimens for the use of cefotaxime in patients with renal impairment are proposed.