Pharmacokinetics of cefodizime following single doses of 0.5, 1.0, 2.0, and 3.0 grams administered intravenously to healthy volunteers

Abstract

Cefodizime is a new expanded-spectrum cephalosporin for parenteral use which possesses a broad antibacterial spectrum and potent antibacterial activity and is stable against most ␤-lactamases. The aim of this study was to assess the pharmacokinetics of cefodizime, administered intravenously, over the dose range of 0.5 to 3.0 g in healthy volunteers. Concentrations of cefodizime in the serum and urine were determined by highperformance liquid chromatography. The area under the concentration-time curve from 0 h to infinity and the amount of drug excreted in urine from 0 to 34 h increased in a linear, dose-dependent manner with increasing doses of antibiotic from 0.5 to 3.0 g. Mean concentrations of cefodizime in plasma at the end of infusion increased from 97 to 440 mg liter ؊1 over the dose range 0.5 to 3.0 g and displayed a slight deviation from linearity at doses in excess of 2.0 g. Total plasma clearance (3.11 liters h ؊1 ), volume of distribution at steady state (10.5 liters), terminal elimination half-life (3.3 h), and renal clearance (1.91 liters h ؊1 ) remained constant over the doses administered. Cefodizime was well tolerated in this study.Cefodizime is a new expanded-spectrum cephalosporin for parenteral use which possesses a broad antibacterial spectrum and potent antibacterial activity and is stable against most ␤-lactamases (5). In addition, it acts synergistically with the host immune system (8, 9).It has been established that there is a linear relationship between the intravenous dose of cefodizime (range, 0.5 to 2.0 g) and the following pharmacokinetic parameters: initial concentration in serum, area under the serum concentration-time curve from 0 h to infinity (AUC 0-ϱ ), and recovery of cefodizime in the urine over 48 h (4). At high concentrations of cefodizime in plasma (Ͼ180 mg liter Ϫ1 ), however, a saturation of the binding of cefodizime to plasma albumin has been observed (1). These high concentrations were observed after a 2.0-g dose for a very short period after infusion. Defining the relationship between the dose and pharmacokinetic parameters of cefodizime over a more extensive dose range was therefore of interest. The aim of this study was to assess the pharmacokinetics of cefodizime, administered intravenously, over the dose range of 0.5 to 3.0 g in healthy volunteers. MATERIALS AND METHODSSubjects and study design. This study was an open, randomized, Latin square crossover study. Twelve healthy, male volunteers aged 18 to 40 years (mean age, 22.3 years), with a mean height of 181 Ϯ 1 cm (range, 175 to 188 cm) and a mean weight of 71 Ϯ 2 kg (range, 60 to 81 kg), were enrolled in the study. Informed written consent was obtained before enrollment. Within the 2 weeks prior to the first dose of cefodizime, a clinical history was taken and a physical examination, including an electrocardiogram, was performed. The following laboratory tests were undertaken: full blood, differential, and platelet count; prothrombin time; and standard biochemical parameters. The results of all of the clinical...

Preparation, physicochemical characterization and biological evaluation of cefodizime metal ion complexes

“…Cefodizime is a broad‐spectrum, third‐generation, parenteral cephalosporin which possesses a prolonged elimination half‐life, of more than 3.5 h 5,6 . The chemical structure of cefodizime disodium salt is shown in Figure 1.…”

Single-dose pharmacokinetics of cefodizime in critically ill elderly patients

“…In the present study, we compared the pharmacokinetics of cefodizime in critically ill elderly patients with previously published data in healthy volunteers [14]. In our study, maximum serum concentrations were similar, although trough levels were slightly elevated.…”

Pharmacokinetics of Cefodizime in Patients with Various Degrees of Renal Failure

“…The increase is consistent with an accumulation of cefodizime. This is predictable since this cephalosporin, like most ß-lactams, is predominantly eliminated by the kidneys [10][11][12]. In fact, we have observed a linear correlation between the creatinine clearance and the total systemic clearance of cefodizime in both healthy subjects and patients suffering from altered renal function.…”