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pubmed-article:8239584pubmed:abstractTextThe possible alterations in the pharmacokinetics and protein binding behavior of the beta-lactam antibiotic cefazolin (CEZ) were investigated in endotoxemic rats induced by Klebsiella pneumoniae O3 lipopolysaccharide (LPS). LPS (250 micrograms/kg of body weight) was infused for 20 to 30 min 2 h before an intravenous administration of CEZ (20 mg/kg). Significant decreases in systemic clearance and renal clearance of CEZ were observed in LPS-treated rats without any changes in fraction of urinary excretion in unchanged CEZ (> 0.8). The volume of distribution at steady state showed a tendency to increase. The protein binding parameters of CEZ, the binding capacity, and number of binding sites on the albumin molecule were decreased by LPS, whereas the dissociation constant did not change. Significant decreases in systemic and renal clearances for unbound CEZ were observed in LPS-treated rats. The glomerular filtration rate estimated as inulin clearance was also decreased by LPS. The ratio of renal clearance of unbound CEZ to glomerular filtration rate (clearance ratio) dropped to 70% of that in control rats, and the net tubular secretion of CEZ was also dramatically reduced. The present study suggests that LPS has an effect on the pharmacokinetics of CEZ by changes which occur in renal handling and protein binding.lld:pubmed
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pubmed-article:8239584pubmed:articleTitleAlterations in pharmacokinetics and protein binding behavior of cefazolin in endotoxemic rats.lld:pubmed
pubmed-article:8239584pubmed:affiliationDepartment of Hospital Pharmacy, Nagoya University School of Medicine, Japan.lld:pubmed
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