CELLULAR PHARMACOLOGY AND OPTIMAL THERAPEUTIC CONCENTRATIONS OF 1‐β‐D‐ARABINOFURANOSYLCYTOSINE 5‘‐TRIPHOSPHATE IN LEUKEMIC BLASTS DURING TREATMENT OF REFRACTORY LEUKEMIA WITH HIGH‐DOSE 1‐β‐D‐ARABINOFURANOSYLCYTOSINE
作者:
William Plunkett,
Stephen Iacoboni,
Michael J. Keating,
期刊:
Scandinavian Journal of Haematology
(WILEY Available online 1986)
卷期:
Volume 36,
issue S44
页码: 51-59
ISSN:0036-553X
年代: 1986
DOI:10.1111/j.1600-0609.1986.tb01590.x
出版商: Blackwell Publishing Ltd
关键词: ara‐CTP;high‐dose ara‐C;individualized therapy;refractory leukemia
数据来源: WILEY
摘要:
ABSTRACTThe pharmacology of 1‐β‐D‐arabinofuranosylcytosine 5′‐triphosphate (ara‐CTP) has been studied in the circulating leukemic blasts of patients with refractory leukemia during therapy with high doses of single‐agent ara‐C. Cellular ara‐CTP was analyzed by high‐pressure liquid chromatography. The median trough concentrations of ara‐CTP in blasts of patients who responded to intermittent high‐dose ara‐C (3 g/m2× 4–12 doses) was 196 μM, whereas 75 μM was the lowest trough ara‐CTP concentration that discriminated between complete remission and treatment failure (p=0.03). The median steady state ara‐CTP concentrations in the blasts of patients who responded to a high dose continuous infusion protocol (2 doses of 3 g/m2every 12 hr followed by a continuous infusion of 330–3000 mg/m2× 4 d) were clustered between 79 and 206 μM. The values of treatment failures were predominantly outside this range (p<0.005). These results suggest that the optimal concentration range for intracellular ara‐CTP in the treatment o
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