cefdinir and Disease-Models--Animal

Acute kidney injury (AKI) was a common organ damage that often occurred after cisplatin. This study was aimed at investigating the pharmacokinetic changes of cefdinir and cefditoren in AKI rats, and elucidating the possible molecular mechanisms.. The renal injury model was established by intraperitoneal injection of cisplatin (12 mg/kg). Plasma creatinine, blood urea nitrogen, the mRNA expression of Kim-1, hematoxylin and eosin staining and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay were used to measure the degree of renal damage. On this basis, the pharmacokinetic changes of cefdinir and cefditoren were investigated in normal and AKI rats. RT-PCR and Western blot were performed to clarify the molecular mechanisms for the changes in the related transporters expression.. The cumulative urinary excretion of cefdinir was significantly decreased and the plasma concentration was remarkably increased in AKI rats. The expression of organic anion transporter 1 (Oat1) and Oat3 in kidney was decreased. However, pharmacokinetics of cefditoren was not influenced. The expression of organic anion-transporting polypeptide 1a1 (Oatp1a1), Oatp1a4, Oatp1b2 and multidrug resistance-associated protein 2 (Mrp2) in liver was unchanged in AKI rats.. The molecular mechanism of decreased expression of Oat1 and Oat3 was achieved through activating p53, and then increasing the expression of Bax and Caspase-3 and down regulating Bcl-2 in AKI rats. On this basis, the cumulative urinary excretion of cefdinir was significantly decreased and the plasma concentration of cefdinir was remarkably increased in AKI rats. However, the pharmacokinetic changes of cefditoren were not observed. Accordingly, cephalosporin antibiotics such as cefditoren should be firstly selected for the treatment in patients with AKI in clinic.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Cefdinir; Cephalosporins; Cisplatin; Disease Models, Animal; Gene Expression Regulation; Kidney; Male; Organic Anion Transport Protein 1; Organic Anion Transporters, Sodium-Independent; Rats, Wistar; Renal Elimination

For conditions such as acute otitis media, in which antibiotic penetration into middle ear fluid (MEF) may be slow or limited, antibiotic plasma levels may not reflect the concentrations at the site of infection that are relevant to clinical outcome. In such cases, a model is needed that will enable prediction of the time course of unbound, pharmacologically active antibiotic levels in MEF. We describe the use of microdialysis as a sampling tool for measurement of unbound antibiotic concentrations in the MEF of the awake, freely moving chinchilla. Results of studies of MEF penetration of the beta-lactam antibiotic, cefdinir, with use of this technique are also described. Preliminary results of studies of the penetration of antibiotics into MEF of the chinchilla appear consistent with clinical findings and suggest that the chinchilla microdialysis model may prove to be a useful tool for predicting antibiotic efficacy in patients.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Cefdinir; Cephalosporins; Chinchilla; Disease Models, Animal; Dose-Response Relationship, Drug; Ear, Middle; Half-Life; Microbial Sensitivity Tests; Microdialysis; Otitis Media; Streptococcus pneumoniae