Squalamine, an aminosterol isolated from the dogfish shark is a water soluble steroid that exhibits potent antibacterial activity against gram-positive and gram-negative bacteria and could potentially be used to inhibit HIV transmission in human females. In this study, a single intravaginal application of radio-labeled Squalamine at 10 mg/animal containing 0.071 mCi/animal 3H drug in 0.5 ml was administered. In order to monitor drug absorption and metabolism, blood samples including a single pre-treatment, all voided urine and excreted feces, including a 24 hour pre-treatment urine and fecal sample were collected at specified intervals to 96 hours post treatment. In addition, at 96 hours post treatment, a vaginal wash was performed to determine the amount of unabsorbed compound. All whole blood, urine and fecal samples were analyzed for tritium and these data used to determine amount of absorbed and metabolized drug. During the study, two of the animals were reported for declining health. After receiving medical treatment one of the animals continued through the end of study, however the other animal did not improve and died. The cause of death was determined to be pancreatitis, hepatic lipidosis, renal cortical pallor, saponification of fat and possible aspiration pneumonia. Findings included low total recovery of tritium, 3.3- 10.5% in the three animals. In addition, no tritium was detected in blood for these animals. A small amount however was detected in the animal that died. Tritium levels remained elevated in the feces and urine for approximately two months. The low recovery of tritium was either a cause of the drug being improperly labeled or rapid hydrolysis of the test article occurred which would lead to rapid production of tritiated free water that could be exchanged with free water throughout the body compartments. *KEY*Aminosterol, Antibacterial, Dogfish shark
NIH ExPorter
NIH ExPorter