Effects of bacterial endotoxin on some metabolites and enzymes in rat serum

The effects of bacterial endotoxins [Escherichia coli, Klebsiella pneumoniae, and Salmonella typhimurium] on glucose and blood urea nitrogen [BUN] levels and aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT] and lactate dehydrogenase [LDH] activities were studied. Three groups of rats were injected [1 mg/kg body weight, i.p.] with three types of bacterial endotoxins [E. coli, K. pneumoniae and S. typhimurium] as a single dose. The control group was injected i.p. [1 mg/kg] in 0.9% normal saline. Blood sampling was performed from the orbital vein plexus after 24 and 72 hr of injection. Glucose level was increased significantly after 24 hr of after each 3 solutions of endotoxin. Its level showed non-significant decrease after 72 hr post-treatment. However, endotoxins caused significant increases in BUN, ASAT and LDH at 24 and 72 hr post-treatment. On the other hand, the ALAT activity was significantly decreased after the referred observation periods of endotoxins injection. The variation in serum glucose level after 24 and 72 hr post-treatment may be referred to different reasons. On the other hand, the increase of BUN concentration may be due to the toxic effect of bacterial endotoxins resembling to that occurring in renal damage and impairment of renal function. However, the changes in serum aminotransferases and LDH activities may be due to endotoxins induced hepatic microcirculatory disturbance and to the subsequent liver injury and tissue hypoxia

study on the possible influence of meloxicam on the pharmacokinetic of a certain narrow therapeutic index drug in rabbits

The present work aimed at evaluating the possible effect of meloxicam on bioavailability and pharmacokinetic of single and repetitive dose of theophylline. The study was conducted on male rabbits. Drugs were administered orally. Theophylline administered as single dose [regimen I] or in concomitant administration with meloxicam following 7 days of meloxicam administration [regimen II]. Multiple dose study was conducted in three groups. The first one for meloxicam, the second for theophylline and the last for their co-administration. Assay of theophylline as well as meloxicam was performed by high performance liquid chromatography. The pharmacokinetic analysis was performed using the non-compartmental analysis. No significant differences between two regimens were found with respect to the main pharmacokinetic parameters of single dose as well as on steady state pharmacokinetic of theophylline according to the bioequivalence guidelines. However, study of within individual variability for Cmax and AUC0-inf revealed that there was a wide variation between individuals with respect to the effect of meloxicam on theophylline pharmacokinetics. The clinical significant of this work should be stressed on theophylline plasma concentration to be monitored in patients receiving concomitant meloxicam and theophylline therapy