Pharmacokinetics of Cefodizime in Normal Individuals and in Patients with Renal Failure

Guinaidy, M. A. El; Nawishy, S; Bary, M.; Sabbour, M. M.

doi:10.1159/000238837

Cited by 7 publications

(4 citation statements)

References 2 publications

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“…This value is consistent with previous observations in a comparable group of patients [5,7]. The observed long half-life may be attributed to the altered renal function, however, we must highlight that El Guinaidy et al [8] have shown a significantly shorter T 1/2· in patients with renal failure, which indicates a faster distribution of cefodizime in these patients, and a longer T 1/2ß , which is in agreement with the significant decrease in total systemic clearance. In any case, the relatively long T 1/2ß may be attributed also to the high protein binding (73%) of cefodizime [9].…”

Section: Discussionsupporting

confidence: 92%

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Pharmacokinetics of Cefodizime in Patients with Various Degrees of Renal Failure

Loffreda¹,

Lampa²,

Lucarelli³

et al. 1999

Chemotherapy

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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.

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Section: Discussionsupporting

confidence: 92%

“…Several studies, involving patients with renal failure and patients treated by continuous ambulatory hemodialysis, looked at the pharmacokinetics of cefodizime [5,7,8]. They demonstrated that the elimination rate of this cephalosporin is proportional to renal function and that renal failure interferes with cefodizime pharmacokinetics.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Cefodizime in Patients with Various Degrees of Renal Failure

Loffreda¹,

Lampa²,

Lucarelli³

et al. 1999

Chemotherapy

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“…It is known that reduced renal function results in a prolongation of elimination of cefodizime [15][16][17]. The majority of our patients presented with mild-to-moderate renal impairment, characterised by a decrease in creatinine clearance.…”

Section: Discussionmentioning

confidence: 86%

Single-dose pharmacokinetics of cefodizime in critically ill elderly patients

Meyer¹,

Traunmueller²,

Bojic³

et al. 2006

International Journal of Antimicrobial Agents

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“…These results are in agreement with, and extend, those obtained by Dagrosa and coworkers, who investigated the pharmacokinetics of cefodizime in healthy male volunteers after single-dose intravenous administration (dose range, 0.5 to 2.0 g) (4). The linear pharmacokinetics of cefodizime facilitate the prediction of the effects of dosage adjustments, for example, in patients with renal or hepatic impairment (6,7).…”

Section: Discussionmentioning

confidence: 99%

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

Lenfant¹,

Namour²,

Logeais³

et al. 1995

Antimicrob Agents Chemother

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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...

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Pharmacokinetics of Cefodizime in Normal Individuals and in Patients with Renal Failure

Cited by 7 publications

References 2 publications

Pharmacokinetics of Cefodizime in Patients with Various Degrees of Renal Failure

Pharmacokinetics of Cefodizime in Patients with Various Degrees of Renal Failure

Single-dose pharmacokinetics of cefodizime in critically ill elderly patients

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

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