Temporal variation in nephrotoxicity of low doses of isepamicin in rats

Abstract

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).

Pharmacologic basis for the treatment of pyelonephritis

“…In animals, higher peak serum levels of aminoglycosides [51][52][53] were found when these drugs were injected during the middle of the rest period. Similar results were observed in the renal levels of these drugs [49,51,[53][54][55]. Table 2 also shows that the maximal serum clearance of aminoglycosides was found when these antibiotics were injected during the middle of the activity period in rodents [52,[56][57][58].…”

“…Yoshiyama et al [53,55] Isepamicin Increase in middle of rest period Song et al [52]; Nakano et al [56] Serum clearance Gentamicin Decrease in middle of rest period Lin et al [57] Tobramycin Decrease in middle of rest period Hosokawa et al [58] Amikacin Decrease in middle of rest period Mesnard-Ricci and White [59] Ampicillin Decrease in middle of rest period Song et al [52]; Nakano et al [56] AUC serum Gentamicin Increase in middle of rest period Lin et al [57] Tobramycin Increase in middle of rest period Hosokawa et al [58] Amikacin Increase in middle of rest period Humans Nakano et al [56] Serum half-life Gentamicin Longer in early evening Yoshiyama et al [60] Isepamicin Longer in late evening Ramesh Rao and Rambhau [62] Sulfamethoxazole Longer in early evening Nakano et al [56] Clearance in serum Gentamicin Higher in morning Yoshiyama et al [60] Isepamicin Higher in morning Nakano et al [56] AUC serum Gentamicin Longer in early evening Yoshiyama et al [60] Isepamicin Longer in late evening Jonkman et al [61] Cefodizime Longer in early evening Sarveshwer Rao et al [63•] Rate of excretion in urine Ciprofloxacin Higher in morning Ramesh Rao and Rambhau [62] Sulfamethoxazole Higher in morning AUC-area under the curve.…”

The effect of fosfomycin on glycopeptide antibiotic-induced nephrotoxicity in rats

“…The renal cortical accumulation of TEIC or VCM was measured by fluorescence polarization immunoassay (TDx; Dainabot, Tokyo, Japan). 12 Histopathological samples were prepared by standard periodic hematoxylin-eosin (HE) staining and were evaluated under a microscope. Sections came from three different regions of the renal cortex of each rat, and five rats per group were used.…”

Chronopharmacology and Antimicrobial Therapeutics

“…In this regard, several studies have reported daily rhythmic fluctuations for both aminoglycoside pharmacokinetics and incidence of toxicity in animals and humans. Chronokinetic experiences demonstrated that clearance is significantly higher and plasma concentrations and AUC are significantly lower when aminoglycosides are administered during the activity period, as compared to those obtained after the drug is administered during the resting period in rats [195][196][197][198]200,207]. Renal distribution may also exhibit daily variations, probably following plasma concentrations, as higher concentrations in the renal cortex of rats treated during the rest period were found when compared to those treated during the active period [200][201][202]204].…”

“…In contrast, daily variations have been proved for both kinetic disposition [142,[187][188][189][190][191][192][193][194][195][196][197] and toxicity [191,[198][199][200][201][202][203][204][205][206][207][208][209][210][211][212] of some antimicrobial drugs.…”