Acute Human Study of Intravenously Infused WR-2823. Volume I.
OKLAHOMA UNIV HEALTH SCIENCES CENTER OKLAHOMA CITY MCALESTER DIV OF CLINICAL PHARMACOLOGY
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WR-2823 has been shown in animal studies to possess alpha-adrenergic blocking activity and increased survival of animals with traumatic, hemorrhagic or endotoxin shock. The purpose of this study was to evaluate its safety, tolerance and effect on blood pressure and heart rate in healthy male volunteers. It was an open study in which the dose was progressively increased by intravenous infusion. Thirty-six subjects participated groups of three subjects were randomly assigned to each of twelve dose levels ranging from 5 to 2,880 mg. The results demonstrated that WR-2823 was free of overt toxicity. However, side effects and evidence of alpha-adrenergic blockade did emerge in a dose related fashion. Unexpected findings were statistically significant decreases in serum calcium and an increase in serum phosphorus and creatinine. These changes were not associated with symptoms and a direct mechanism was not elucidated. There were no other laboratory findings thought to be drug related.