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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Preclinical antitumor activity and pharmacological properties of deoxyspergualin.

A new antibiotic, deoxyspergualin (DSG), demonstrated antitumor activity against L1210 leukemia in mice. The life span of mice bearing either i.p. or s.c.-implanted L1210 increased greater than 150% following i.p. administration of 25 mg/kg DSG on days 1-9. Activity obtained with i.p. bolus treatments was schedule dependent. The tumor burden in mice bearing the s.c. implanted L1210 was reduced by 4-6 log10 units at the end of treatment when DSG was administered every 3 h for 8 injections on days 1, 5, and 9. By contrast, single injections of DSG on days 1, 5, and 9 allowed the tumor burden to increase at least 100-fold during treatment and daily single injections for 9 days reduced the tumor burden by 2 log10 units. The therapeutic advantage for i.p.-implanted L1210 of maintaining plasma concentrations of DSG was indicated further by infusion studies using s.c.-implanted Alzet osmotic pumps. Tumor burden was reduced by 3.5 and 6 log10 units following s.c. bolus treatments every 3 h on day 1 and a 24 h-infusion, respectively. The optimal infusion time for an infusion rate in mice of 179 mg/kg/day appeared to be 72 h. Pharmacokinetic studies following bolus i.v. injection revealed a rapid plasma clearance of parent drug (20.8 ml/min/kg) and a beta half-life of approximately 12 min. The bolus dose kinetics was used to predict the steady state plasma concentrations resulting from s.c. infusion; good agreement was observed between predicted values and experimental results. Based on these preclinical data, DSG has been developed to clinical trial. Initial Phase I protocols involve a 120-h infusion schedule.[1]

References

  1. Preclinical antitumor activity and pharmacological properties of deoxyspergualin. Plowman, J., Harrison, S.D., Trader, M.W., Griswold, D.P., Chadwick, M., McComish, M.F., Silveira, D.M., Zaharko, D. Cancer Res. (1987) [Pubmed]
 
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