Pharmacokinetics of cefotaxime in subjects with normal and impaired renal function

Abstract

The pharmacokinetics of cefotaxime was investigated in 6 healthy subjects and in 22 uraemic patients with various degrees of renal insufficiency. After i.v. bolus injection of a single 15 mg/kg dose, pharmacokinetic data were calculated using a three-compartment open body model. <it>In healthy subjects</it>, after i.v. injection, the mean terminal serum half-life <it>T</it>½ β was 1.44 ± 0.45 h and apparent volume of distribution V<inf>darea</inf> was 34.23 ± 9.19 1/1.73 m2. After a similar i.m. dose, the mean peak serum level was 25.32 ± 3.94 mg/l, the elimination T½ was 1.07 ± 0.14 h and bioavailability was 91.5±14.8 %. Fifty to sixty per cent of the injected dose was recovered unchanged in 24 h urines. Renal and serum clearances were 170 and 280 ml/min/1.73 m2, respectively. <it>In uraemic patients</it>, after a single 15 mg kg i.v. dose, <it>T</it>½ β increased in relation to degree of renal impairment up to 10.81 ± 3.23 h in patients with creatinine clearance (C<inf>cr</inf>) lower than 8 ml/min/1.73 m2. In haemodialysis patients, <it>T</it>½ β was out of dialysis 8.96 ± 6.47 h and on a 4 to 6 h-dialysis session 1.98 ± 0.72 h. 62.3 ± 17.4 % of the drug was extracted by dialysis. The apparent volume of distribution was not significantly modified by renal insufficiency. Relationships between pharmacokinetic data (<it>T</it>½ β,) and biological parameters of renal function (serum creatinine, C<inf>cr</inf>) provide a basis for dosage adjustment in renal failure.