Subacute toxicity studies with prostaglandin E<sub>1</sub> (PGE<sub>1</sub>) in laboratory animal species
Rao, K. S.; Reno, F. E.; Rao, K. S.; Searle Laboratories; Reno, F. E.; Hazleton Laboratories America
Журнал:
Journal of Toxicology and Environmental Health
Дата:
1976
Аннотация:
Prostaglandins are a group of modified hydroxy fatty acids with a wide distribution in mammalian tissues. They possess a wide range of potent biological activities and promise to be useful clinically in areas as diverse as the treatment of asthma and termination of pregnancy. In spite of the voluminous scientific literature on prostaglandins, there is little information on the relative safety of these agents in animals. In the present study subacute effects of prostaglandin E<sub> 1 </sub> (PGE<sub> 1 </sub>), a representative of the series, were studied in albino rats and Beagle dogs. The compound was dissolved in phosphate buffer and administered by continuous intravenous infusion for 3–6 hr daily, at dose levels up to 2.0 μg/kg/min for 14 consecutive days. Conventional physical, cardiovascular, hematologic, clinical chemical, and postmortem examinations were performed. Dogs exhibited occasional episodes of stupor and/or excitement and emesis. In rats no compound‐related physical signs were observed. Cardiovascular parameters and hematology findings were unremarkable. A decrease in blood glucose was observed sporadically in both rats and dogs. Postmortem findings, gross and microscopic, were unremarkable. It is concluded that daily iv infusion of PGE<sub> 1 </sub> up to 2.0 μg/kg/min for 14 consecutive days to rats and dogs causes no biologically meaningful detrimental effects.
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