NEPHROTOXICITY OF CEFPIROME SULFATE IN RABBITS : Single and Multiple Intravenous Administration

Deki, Toshiaki; Matsuoka, Akio; Marutani, Kiyoshi; NAKAGAWA, Tsugio; MASUDA, Kumiko; MATSUZAWA, Tadanori; Horiuchi, Kazuhiro; Ohishi, Takao; OHTANI, Takehiko; Niki, Rikio; Kumagai, Yasunori

doi:10.2131/jts.15.supplementiii_173

Cited by 5 publications

(8 citation statements)

References 1 publication

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“…This might be attributed to the progressive cellular and tubular dysfunction manifested histopathologically in the present work. This was consistent with that recorded in rabbits following administration of both cefpirome[23] and after oral dosing of cefmtaline, urinary protein was detected. [25]…”

Section: Discussionsupporting

confidence: 91%

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Nephrotoxicity of cefepime: A new cephalosporin antibiotic in rats

Elsayed¹,

Elkomy²,

Gab-Allah

et al. 2014

Journal of Pharmacology and Pharmacotherapeutics

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Objectives:To investigate the nephrotoxic effect and biochemical alterations induced by cefepime in rats.Materials and Methods:Cefepime was administered intramuscularly at doses of 45, 90 and 180 mg/kg b.wt. once daily for 5 consecutive days. The serum and urine samples were used for quantitative determination of urea, creatinine, glucose, total protein, calcium, sodium and potassium. The histopathological examination of kidney tissues was performed 1, 4 and 8 days after the last dose of cefepime administration.Results:Cefepime induced a significant increase in the total amount of urine per day, urea and creatinine concentration in the serum and urine and significant decrease in their clearance. Cefepime also caused a significant gluocosuria and proteinuria and significant decrease in their serum concentrations. The effect of cefepime on serum and urine concentrations of calcium, sodium and potassium were also determined. Cefepime injection in the three tested doses caused renal tubular, glomerular and vascular changes. The severity of these changes was dose dependent. In conclusion, these results suggest a possible contribution of cefepime in the nephrotoxicity and biochemical alterations, especially at high doses. Therefore, the renal functions should be monitored during the cefepime therapy.

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Section: Discussionsupporting

confidence: 91%

“…This result was agreeable with that cefodizime increased serum creatinine[22] and after administration of cefpirome in rabbits. [23] Cefamandole significantly increased serum creatinine and decreased it in urine and also creatinine clearance was decreased. [18] Cefepime elevated serum creatinine and caused interstitial nephritis.…”

Section: Discussionmentioning

confidence: 99%

Nephrotoxicity of cefepime: A new cephalosporin antibiotic in rats

Elsayed¹,

Elkomy²,

Gab-Allah

et al. 2014

Journal of Pharmacology and Pharmacotherapeutics

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“…After pathological changes appeared and influenced the function of glomerulus or tubules, large protein gathered to form cylindruria. This was also consistent with other researches following administration of cefpirome, urinary protein was detected (Deki et al, 1990).…”

Section: Discussionsupporting

confidence: 92%

The pharmacokinetics change of cefepime after Shuanghuanglian injection administration in subjects with the renal damage

Chen

Min

Zhao

et al. 2015

Drug and Chemical Toxicology

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Shuanghuanglian injection (SHLI) has been widely used for administration with cephalosporin in China for long time. The objective of this study was to evaluate the pharmacological properties and biochemical changes of cefepime combined with SHLI. The SD rats included were received either an intravenous (iv. 4 mL/kg) dose of normal saline, or intravenous (iv. 0.74, 0.37, 0.185 g/kg, respectively) doses of SHLI once daily for 7 days. After last administration, cefepime (0.41 g/kg) was intravenous injected to the animals. The serum and urine samples were acquired and stored at 4 °C. They were used for quantitative determination of urea nitrogen (BUN), creatinine (CRE), urine protein, alkaline phosphatase (ALP) and N-acetyl-B-d-glucosaminidase (NAG). At different time points, the levels of cefepime in rat plasma were estimated for pharmacokinetic measures by HPLC. Aspirin was selected as internal standard (IS). The results showed that there were positive effects by increasing the total amount of CRE, BUN, NAG and urine protein (p < 0.01 or <0.05) and decreasing the levels of ALP (especially the high dose group of SHLI with cefepime) (p < 0.01). Besides, the pharmacokinetic results indicated that cefepime was distributed as non-compartment model after intravenous administration. Compared with the corresponding values for the compounds given alone, the area under the blood drug concentration time curve (AUC0-t and AUC0-∞) was better increased in middle- and high-dose groups (pall < 0.01), the mean residence time (MRT) of cefepime was larger (pall < 0.01) and the total clearance (CL) was lower at different levels. The results mean that the duration and concentration of cefepime could be prolonged and the clearance reduced while in combination with SHLI. Furthermore, the cefepime in the three tested doses caused changes of renal tubular epithelial cells while the severity of changes mainly dependent on the specific doses. In conclusion, the results above-mentioned suggest a possible contribution of drug combination in the nephrotoxicity and biochemical alterations especially at high doses. Further, monitoring measures for the renal functions are warranted to evaluate during the combination of these two drugs.

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“…This might be attributed to the progressive cellular and tubular dysfunction manifested histopathologically (El-Sayed et al, 2014). This was consistent with that recorded in rabbits following administration of both cefpirome (Deki et al, 1990) and after oral dosing of cefmtaline, urinary protein was detected (Kato et al, 2001).…”

Section: Effect On Serum Albuminsupporting

confidence: 82%

Effects of Cefepime on Serum Liver and Kidney Functions in Rabbits

Helal

Said

El-DinShams

et al. 2021

Zagazig Journal of Agricultural Research

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This study aimed to determine the effect of cefepime on different liver and kidney functions of healthy rabbits (35days/1kg) were injected with singular intramuscular dose once daily for 5 successive days with 75 mg/kg body weight. Twenty-four healthy rabbits of the same sex were divided into two groups (n=12). First group was injected with distilled water (control) and second group was injected with 75 mg/kg once daily for 5 successive days. Blood samples were taken at (1 st , 3 rd , 7 th and 14 th day) without anticoagulant, centrifuged and frozen. Samples were analyzed and the results indicated that there was non-significant effect on liver functions as there was no change in each of the serum AST, ALT, ALP, total protein, and total albumin. The results indicated also that there was insignificant effect of cefepime on kidney functions, in terms of insignificant difference of serum urea and concentration and creatinine levels, meaning the safety of the drug on public health.

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NEPHROTOXICITY OF CEFPIROME SULFATE IN RABBITS : Single and Multiple Intravenous Administration

Cited by 5 publications

References 1 publication

Nephrotoxicity of cefepime: A new cephalosporin antibiotic in rats

Nephrotoxicity of cefepime: A new cephalosporin antibiotic in rats

The pharmacokinetics change of cefepime after Shuanghuanglian injection administration in subjects with the renal damage

Effects of Cefepime on Serum Liver and Kidney Functions in Rabbits

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