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Zaharko DS, Covey JM, Kelley JA. Plasma kinetics and effects of 5,6-dihydro-5-azacytidine in mice and L1210 tumor. Invest New Drugs. 1985;3(1):35-41doi: 10.1007/BF00176822.
Zaharko, D. S., Covey, J. M., & Kelley, J. A. (1985). Plasma kinetics and effects of 5,6-dihydro-5-azacytidine in mice and L1210 tumor. Investigational new drugs, 3(1), 35-41. https://doi.org/10.1007/BF00176822
Zaharko, D S, et al. "Plasma kinetics and effects of 5,6-dihydro-5-azacytidine in mice and L1210 tumor." Investigational new drugs vol. 3,1 (1985): 35-41. doi: https://doi.org/10.1007/BF00176822
Zaharko DS, Covey JM, Kelley JA. Plasma kinetics and effects of 5,6-dihydro-5-azacytidine in mice and L1210 tumor. Invest New Drugs. 1985;3(1):35-41. doi: 10.1007/BF00176822. PMID: 3838737.
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Invest New Drugs. 1985;3(1):35-41. doi: 10.1007/BF00176822.

Plasma kinetics and effects of 5,6-dihydro-5-azacytidine in mice and L1210 tumor.

Investigational new drugs

D S Zaharko, J M Covey, J A Kelley

PMID: 3838737 DOI: 10.1007/BF00176822

Abstract

The plasma kinetics of 5,6-dihydro-5-azacytidine (DHAC) was determined in mice using an HPLC method following an intravenous dose of 2000 mg/kg (LD10). Pharmacokinetic parameters calculated from these single dose data were sufficient to predict steady state plasma concentrations produced by s.c. infusion of DHAC. Lethal toxicity (LD66) occurred at an infusion rate of 37 mg/kg/h (111mg/m2/h), corresponding to a plasma steady-state DHAC concentration 38 +/- 14 micrograms/ml when the infusion time was 96 h; no lethality occurred at infusion times of 72 h or less. In vitro clonogenic assays and in vivo therapeutic experiments with L1210 tumor indicated that increasing the exposure time at concentrations near 25 micrograms/ml from 24 to 72 h increased the cell kill only slightly. The maximum log cell kill of L1210 estimated from either in vitro or in vivo data was 1.5 logs.

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