Pharmacokinetics of TSC and the treatment of hypoxic states

Previous research has shown that the drug trans sodium crocetinate (TSC) increases whole-body oxygen consumption in hemorrhaged rats. TSC has also shown beneficial effects in treating hemorrhagic shock in swine. The best method of drug delivery, however, has been limited by a lack of knowledge of the pharmacokinetics of TSC.; In the current study, the pharmacokinetics of TSC have been studied using a rat model. Following intra-arterial injection, it was shown that the drug plasma concentration declined in a multiexponential fashion; the drug being rapidly distributed followed by a slower elimination phase. Comparison of drug concentration data over a dosage range suggests that the kinetics of TSC may be dose dependent. TSC was also administered via pulmonary and intramuscular routes in rats as well as intravenous injection in swine, and these data are compared to the intra-arterial data in rats. To further extend the pharmacokinetic analysis, the drug was administered by intra-arterial, pulmonary, and intramuscular routes in hemorrhaged rats in order to determine if the rate of clearance and absorption of TSC are altered when the blood volume is decreased.; TSC was administered as a treatment for two hypoxic states; hemorrhagic shock and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Pulmonary and intramuscular injection routes for TSC administration in hemorrhaged rats were studied, and both methods were found to increase the mean arterial pressure, which is a strong indicator that the treatment is efficacious. For the treatment of respiratory insufficiencies, an oleic acid model of acute lung injury was used. Following TSC treatment in this model of lung injury, the mean arterial P02 increased, suggesting that oxygen transport from the lungs to the red blood cells was enhanced by TSC.