9-beta-D-arabinofuranosyladenine 5'-phosphate metabolism and excretion in humans.
9-beta-D-Arabinofuranosyladenine (ara-A) was converted chemically to the 9-beta-D-arabinofuranosyladenine 5'-phosphate (ara-A-5'-P) and administered i.v. to four cancer patients in seven experiments. Urinary excretion and plasma levels of radioactivity were monitored for 24 hr in each case. Radioactivity present as unchanged ara-A-5'-P, ara-A, and the deamination product of ara-A, 9-beta-D-arabinofuranosylhypoxanthine, was determined. Excretion was, as in earlier studies with ara-A, given i.v., largely as 6-beta-D-arabinofuranosylhypoxanthine. However, in contrast to the 88 to 97% excretion of ara-A and products in 24 hr when ara-A was given by i.v. push, excretion was 41.47 to 79.1% in 24 hr when ara-A-5'-P was given. With the exception of one experiment at a low dose, where plasma ara-A levels were significant for 6 hr, the plasma levels of ara-A were sustained at significant levels for 24 hr after a single dose of ara-A-5'-P. The doses of ara-A-5'-P given were well tolerated by the four patients. Indications are that this derivative provides important advantages (solubility and sustained blood levels) over ara-A.
D000230:Adenocarcinoma / Q000188:drug therapy; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D002277:Carcinoma / Q000188:drug therapy; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D013997:Time Factors; D014740:Vidarabine / Q000378:metabolism / Q000627:therapeutic use
D000249:Adenosine Monophosphate; D014740:Vidarabine