Pharmacokinetic study of fludarabine phosphate (NSC 312887)

Summary Characterization of the pharmacokinetics of 2-FLAA has been completed in seven patients receiving 18 or 25 mg/m² daily x5 of 2-FLAMP over 30 min. Assuming 2-FLAMP was instantaneously converted to 2-FLAA, the plasma levels of 2-FLAA declined in a biexponential fashion. Computer fitting of the plasma concentrationtime curves yielded an average distribution half-life (t1/2) of 0.60 h and a terminal half-life (t1/2) of 9.3 h. The estimated plasma clearance was 9.07±3.77 l/h per m² and the steady state volume of distribution, 96.2±26.0 l/m². There was a significant inverse correlation between the area under the curve (AUC) and absolute granulocyte count (r=-0.94, P<0.02). A relationship between creatinine clearance and total body clearance was noted, but was not statistically significant (r=0.828; P<0.1). Aproximately 24%±3% of 2-FLAA was excreted renally over the 5-day course of drug administration.Abbreviations used 2-FLAA-9--D arabinofuranosyl-2-fluoroadenine - 2-FLAMP the 5'-monophosphate of 2-FLAA, also known as fludarabine phosphate - AUC area under the curve - AGC absolute granulocyte count - TPC total plasma clearance - Vd_ss volume of distribution at steady state - Vd volume of distribution - Creat Cl creatinine clearance - SGOT serum glutamic-oxaloacetic transaminase - WBC peripheral white blood cell count This study was supported by contract NCI N01-CM-27542, NIH grant RR-01346 and by the VA Research Service.