isepamicin and Kidney-Diseases

The safety profile of isepamicin has been assessed from a series of phase II and III clinical trials. A total of 1243 patients were randomised to treatment with isepamicin, mainly administered once daily at a dose of 15 mg/kg or 8 mg/kg depending on the severity of infection. A small proportion of patients were randomised to isepamicin at a dosage of either 7.5 mg/kg twice daily or 4 mg/kg twice daily. In the majority of studies, isepamicin was compared with a standard twice-daily dosing regimen of 7.5 mg/kg amikacin = (n - 552). The clinical studies included patients with a variety of bacterial infections, including lower respiratory tract, urinary tract, intra-abdominal and skin and skin structure infections. The study aminoglycosides were co-administered with other antimicrobial agents in line with normal clinical practice depending on the site, nature and severity of infection. Most patients received isepamicin or amikacin as a 30-minute intravenous infusion and a small proportion of patients with less severe infections received intramuscular injections. The mean duration of treatment was nine days for both the isepamicin and amikacin treatment groups, and was similar for patients with both severe and less severe infections. Overall, the proportion of patients reporting any adverse event was comparable between the isepamicin (13%) and amikacin (11%) groups. No individual adverse event was reported in more than 2% of patients, the most commonly reported events being phlebitis, rash, headache and renal compromise. The frequency of adverse events was not influenced by treatment duration, age or gender. Treatment-related adverse events which were considered severe or life-threatening were reported in 1.8% of patients receiving isepamicin and 2.0% of patients receiving amikacin. Two per cent of patients in each treatment group discontinued the study because of adverse events and 2% of patients in each treatment group died during treating. Four per cent of patients in each treatment group died within 30 days after the end of treatment. Changes in laboratory tests were similar in both treatment groups; few changes were considered by the investigators to be treatment-related. Increases in serum creatinine indicative of possible renal compromise occurred in 4.6% of isepamicin and 5.1% of amikacin patients. The occurrence of ototoxicity as measured by standard frequency pure tone audiometry was low. In summary, isepamicin is a sell-tolerated aminoglycoside with

Topics: Adult; Aged; Anti-Bacterial Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Creatinine; Dose-Response Relationship, Drug; Drug Administration Routes; Female; Gentamicins; Hearing Disorders; Humans; Kidney Diseases; Liver; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

The safety profile of isepamicin has been assessed from a series of phase II and III clinical trials. A total of 1243 patients were randomised to treatment with isepamicin, mainly administered once daily at a dose of 15 mg/kg or 8 mg/kg depending on the severity of infection. A small proportion of patients were randomised to isepamicin at a dosage of either 7.5 mg/kg twice daily or 4 mg/kg twice daily. In the majority of studies, isepamicin was compared with a standard twice-daily dosing regimen of 7.5 mg/kg amikacin = (n - 552). The clinical studies included patients with a variety of bacterial infections, including lower respiratory tract, urinary tract, intra-abdominal and skin and skin structure infections. The study aminoglycosides were co-administered with other antimicrobial agents in line with normal clinical practice depending on the site, nature and severity of infection. Most patients received isepamicin or amikacin as a 30-minute intravenous infusion and a small proportion of patients with less severe infections received intramuscular injections. The mean duration of treatment was nine days for both the isepamicin and amikacin treatment groups, and was similar for patients with both severe and less severe infections. Overall, the proportion of patients reporting any adverse event was comparable between the isepamicin (13%) and amikacin (11%) groups. No individual adverse event was reported in more than 2% of patients, the most commonly reported events being phlebitis, rash, headache and renal compromise. The frequency of adverse events was not influenced by treatment duration, age or gender. Treatment-related adverse events which were considered severe or life-threatening were reported in 1.8% of patients receiving isepamicin and 2.0% of patients receiving amikacin. Two per cent of patients in each treatment group discontinued the study because of adverse events and 2% of patients in each treatment group died during treating. Four per cent of patients in each treatment group died within 30 days after the end of treatment. Changes in laboratory tests were similar in both treatment groups; few changes were considered by the investigators to be treatment-related. Increases in serum creatinine indicative of possible renal compromise occurred in 4.6% of isepamicin and 5.1% of amikacin patients. The occurrence of ototoxicity as measured by standard frequency pure tone audiometry was low. In summary, isepamicin is a sell-tolerated aminoglycoside with

Topics: Adult; Aged; Anti-Bacterial Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Creatinine; Dose-Response Relationship, Drug; Drug Administration Routes; Female; Gentamicins; Hearing Disorders; Humans; Kidney Diseases; Liver; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

The protective effect of ceftriaxone on isepamicin-induced nephrotoxicity was investigated. For 14 d, Wistar rats were administered either ceftriaxone 100 mg/kg intraperitoneally, isepamicin 300 mg/kg subcutaneously, or ceftriaxone isepamicin in combination. The animals given 300 mg/kg of isepamicin showed a significant increase in urine NAG (N-acetyl-beta-D-glucosaminidase) levels as compared with the control animals which received saline (p<0.01). However, the increase in NAG level was markedly less when isepamicin was administered in combination with ceftriaxone (p<0.01). Ceftriaxone alone had no effect on urine NAG activity. Serum creatinine levels were significantly higher in animals treated with isepamicin alone than in control animals (p<0.01) or animals receiving the isepamicin ceftriaxone combination (p<0.01). After 14 d of treatment, ceftriaxone had not accumulated in renal tissue, but it did reduce the renal intracortical accumulation of isepamicin (p<0.01). Histopathologically, ceftriaxone induced very few cellular alterations and considerably reduced the manifestation of typical signs of isepamicin nephrotoxicity. This investigation demonstrates that ceftriaxone protects animals against isepamicin-induced nephrotoxicity.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Creatinine; Gentamicins; Hexosaminidases; Kidney Cortex; Kidney Diseases; Male; Rats; Rats, Wistar

The temporal variation in the nephrotoxicity of low doses of isepamicin was studied in male Sprague-Dawley rats treated with a single daily intraperitoneal injection of saline (NaCl, 0.9%) or isepamicin (80 mg/kg of body weight) at either 0800, 1400, 2000, or 0200 h for 4 and 10 days. On day 10, the cellular regeneration (incorporation of [3H] thymidine into DNA of renal cortex) and cortical accumulation of isepamicin were significantly higher in animals treated at 1400 h than at 0200 h (P < 0.01). Immunogold labeling studies showed that isepamicin was essentially localized in the lysosomes of proximal tubular cells in all treated groups, but the density of the gold particles over the lysosomes was higher in animals treated at 1400 than at 0200 h. The results of the present study show that the renal toxicity of isepamicin was maximal at 1400 h (midlight period) and minimal at 0200 h (middark period).

Topics: Animals; Anti-Bacterial Agents; Body Weight; Circadian Rhythm; Gentamicins; Immunohistochemistry; Injections, Intraperitoneal; Kidney Cortex; Kidney Diseases; Kidney Tubules, Proximal; Male; Microscopy, Electron; Rats; Rats, Sprague-Dawley; Regeneration; Thymidine; Time Factors

Nephrotoxicity was more marked in rats receiving isepamicin at midlight than at middark. And, the once-daily administration at middark induced a lesser degree of nephrotoxicity than the twice-daily injection, which indicates that the once-daily treatment therapy may have potential value in the clinical use of aminoglycosides.

Topics: Animals; Anti-Bacterial Agents; Circadian Rhythm; Gentamicins; Injections, Subcutaneous; Kidney Diseases; Rats; Rats, Wistar

The nephrotoxic potentials of the new aminoglycoside SCH 21420 and amikacin were compared in a rat model. Groups of rats received 100, 200, 300, or 600 mg of either drug per kg per day for 14 days. Enzymuria, urine osmolality, protein excretion, and blood urea nitrogen were monitored at periodic intervals, whereas creatinine clearance and pathological changes were determined at sacrifice. Amikacin caused more enzymuria at the two lower doses as well as greater proteinuria and blood urea nitrogen elevations at the highest dose than did SCH 21420 (P less than 0.05). Pathological changes were more severe with amikacin than with SCH 21420 at the three lower doses (P less than 0.05); however, at the 600 mg/kg per day dose, the pathological scores and creatinine clearances of animals receiving either drug were not significantly different (P greater than 0.05).

Topics: Amikacin; Animals; Creatinine; Enzymes; Gentamicins; Kanamycin; Kidney Diseases; Male; Proteinuria; Rats; Time Factors