PT  - JOURNAL ARTICLE
AU  - D H Ho
AU  - N Brown
AU  - J R Lin
AU  - W Covington
AU  - R A Newman
AU  - M Raber
AU  - R Amato
AU  - S Schmidt
AU  - I H Krakoff
TI  - Clinical pharmacology of 1-beta-D-arabinofuranosyl-5-azacytosine (fazarabine) following 72-hour infusion.
DP  - 1991 May 01
TA  - Drug Metabolism and Disposition
PG  - 643--647
VI  - 19
IP  - 3
4099  - http://dmd.aspetjournals.org/content/19/3/643.short
4100  - http://dmd.aspetjournals.org/content/19/3/643.full
SO  - Drug Metab Dispos1991 May 01; 19
AB  - The clinical pharmacology of fazarabine (1-beta-D-arabinofuranosyl-5-azacytosine), a structural analogue of 1-beta-D-arabinofuranosylcytosine (ara-C) and 5-azacytidine, was assessed in 14 patients with various malignancies during a phase I trial. Since the starting dose for the protocol was low (0.2 mg/m2/hr over a 72-hr continuous iv infusion), a radioimmunoassay (RIA) using commercially available ara-C antibody and [3H]ara-C was developed to measure the anticipated low plasma drug levels. The assay could be used to measure fazarabine accurately in plasma and urine with a sensitivity of 0.08 ng/ml. The RIA does not require extraction of samples. Using both RIA and HPLC, similar results were obtained in plasma samples from a patient receiving a high dose (180 mg/m2/hr) of fazarabine. The assay is simple, sensitive, reproducible, and specific. Following the infusion, plasma levels declined triphasically with a terminal half-life of 5.7 +/- 2.0 hr. The AUC was linearly related to dose. When the various doses were normalized to 1.75 mg/m2/hr (the maximum tolerated dose as determined from the phase I trial) the mean AUC value was 4232 +/- 987 (ng/ml)hr. Plasma steady-state drug levels (CPss) were achieved in 2-4 hr and were linearly dependent to dose. Also, when normalized, the mean CPss was 58 +/- 13 ng/ml, which is within the reported concentration range necessary for inhibiting malignant cell growth. Total clearance was rapid, 528 +/- 138 ml/(m2.min), and not dose-related.