ABSTRACT
Clmetldlne and ranitidine are used In patients with lifethreathenlng gram-negative Infections, endotoxemla and acute stress erosions. Disposition kinetics of clmetldlne and ranitidine In endotoxin pretreated rats was Investigated. The H2 antagonists were administered intravenously 24 h after endotoxin (10 mg/kg) pretreatment. This endotoxin dosage resulted in 50% mortality in rats. Blood samples (0.25 ml) were collected at different timed intervals. No significant differences were observed in plasma clearance, half-life and volume of distribution between endotoxin pretreated and control rats. Clmetldlne is eliminated extensively by the renal route in animals and man with metabolism being a minor process. Ranitidine is metabolized to a large extent (70%) in rats, while in humans this represents a minor process. No significant changes in clmetldlne and ranitidine disposition parameters in endotoxin pretreated rats were observed. These results suggest that clmetldlne and ranitidine may be used in normal dosages in endotoxemla patients since their pharmacokinetic parameters would not be affected under these circumstances.