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Articles by P.R. Mishra
Total Records ( 1 ) for P.R. Mishra
  V. Prasad , V. Jain and P.R. Mishra
  The present study was aimed to measure absorption and disposition of cyclosporine in endotoxin pretreated rats. Cyclosporine (Sandimmune, 10 mg kg-1) was orally administered with and without a concomitant dose of endotoxin (5 mg kg-1) i.p. to rats. Cyclosporine concentrations in blood samples were determined by HPLC UV detector. The pharmacokinetic parameters were calculated by noncompartmental analysis using WINNONLIN. The pretreatment of endotoxin in rats significantly increased cyclosporine AUC0-t (area under the concentration-time curve from time zero to the last point) by 33% in rats, indicating that the rats pretreating with endotoxin significantly increased cyclosporine oral bioavailability. In vitro absorption study was done to assess the effect of endotoxin on cyclosporine absorption. However, the significant increase in permeation drug into serosal side was noticed in rats, when pretreated with endotoxin, thus the inverted sac study also supported the finding of endotoxin inhibited the function of intestinal P-gp thus making cyclosporine more absorbed into lumen. The increased absorption of cyclosporine in both in vitro and in vivo may be due to inhibitory activity of endotoxin on intestinal P-gp and Cytochrome P4503A. This is significant in cases when cyclosporine was administered as immunosuppressant agent in patients suffering from septimea. A paired Student`s t-test was conducted for statistical comparison in all experiments.
 
 
 
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