Pharmacokinetics of Cefodizime in Patients with Various Degrees of Renal Failure

Abstract

The pharmacokinetics of cefodizime, a new expanded-spectrum cephalosporin for parenteral use, was studied in 45 subjects with various degrees of renal failure. Patients were divided into five groups according to the following creatinine clearances: group I >80 ml/min; group II <80–30 ml/min; group III <30–15 ml/min; group IV <15–5 ml/min and group V <5 ml/min. Cefodizime was administered as a 1 g i.v. bolus. Plasma and urinary concentrations of cefodizime were determined by high-performance liquid chromatography, using for detection UV absorbance. The following pharmacokinetic parameters were calculated: maximum plasma concentration (C_{5 min}), area under the plasma concentration-time curve (AUC), terminal half-life (T_1/2), terminal rate constant (λ-z), total clearance (Cl_t), volume of distribution (V_d), mean residence time (MRT), urine data-derived terminal half-life (T_{1/2 r}), renal clearance (Cl_r). The results of this study showed that renal failure induced changes in cefodizime pharmacokinetics. Our data demonstrated a close correlation between degree of renal impairment and pharmacokinetic changes. The maximum plasma concentration (C_{5 min}) was higher in patients with renal failure; T_1/2 was increased; AUC also increased from 470.40 ± 17.80 mg·h/l in the control group to 1,562.30 ± 170.8 mg·h/l in group V. Moreover, no side effect was observed after treatment with 1 g i.v. of cefodizime. Although renal failure induces significant changes of cefodizime pharmacokinetics, the drug was well tolerated and only in patients with severe renal insufficiency we advise to monitor the interval dose of cefodizime or adjust doses to renal function.