Abstract
The cytotoxic activity of araC is dependent on the intracellular accumulation of the active 5'-triphosphate araCTP. Using HPLC, it was possible to study the pharmacology of araCTP in circulating blasts of patients being treated with high-dose araC (3 g/m2 q 12 h × 4-12 doses). The rate of araCTP elimination (t½) from leukemic cells and the area under the intracelluar araCTP concentration × time curve were strongly correlated with clinical response. Therefore it was of interest to determine whether simultaneous administration of an additional antileukemic drug, m-AMSA, would alter the cellular metabolism of araCTP during combined therapy. Determinations of the t½ and AUC of araCTP after successive doses of araC alone to 5 patients indicated a slight increase (10-15%) in each parameter. Prospective studies of araCTP metabolism were conducted in the circulating blasts of 6 additional patients who received araC alone followed 12 hr later by simultaneous administration of araC and m-AMSA (30 mg/m2 over 1 hr). Thus, the cellular pharmacokinetics of araCTP after araC alone served as the control for the combination. Mean decreases of 9% in the t½ and 10% in the AUC were observed. These results suggest that coadministration of m-AMSA with araC may adversely affect the cellular metabolism of araCTP in circulating leukemic blasts.
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Plunkett, W., Iacoboni, S., Danhauser, L. et al. CELLULAR PHARMACOKINETICS OF araCTP DURING THERAPY OF REFRACTORY ACUTE LEUKEMIA WITH araC: EFFECT OF m-AMSA: 163. Pediatr Res 19, 771 (1985). https://doi.org/10.1203/00006450-198507000-00183
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DOI: https://doi.org/10.1203/00006450-198507000-00183
