Hypotensive Action of Ellipticine Hydrochloride Citrate Formula, Lot 72-264, NSC 71795 in a Beagle Dog and a Rhesus Monkey Following I.V. Infusion.

摘要

Ellipticine hydrochloride, Lot no.72-264 when formulated in citric acid sodium citrate buffer, pH 3.3, Lot no. 72-265, was hypotensive in both the beagle dog and Rhesus monkey when administered in a dog in a dose of 18mg/kg given by infusion I.V. over periods of 15 and 120 minutes and when administered I.V. to the monkey in a dose of 9mg/kg infused over a period of one hour. In the Rhesus monkey there was a further fall in systemic blood pressure during the one hour post infusion period with no signs of recovery. This failure of recovery of the blood pressure was also noted during the 2 hour infusion study in the beagle dog. These findings are completely at variance with our previous studies on the hypotensive action of Ellipticine which showed that I.V. administration of the drug in 15 minute and 2 hour infusions obviated the hypotensive effect produced by administration of the drug as a bolus. In vitro a concentration of 0.01mg/m1 of this formulation was compatible with dog, monkey and human blood, but concentrations of 0.1 and 10mg/m1 were incompatible as evidenced by hemolysis or clumping.