BIOAVAILABILITY AND BACTERIAL-DEGRADATION OF RECTALLY ADMINISTERED 2-CHLORO-2'-DEOXYADENOSINE

2-Chloro-2'-deoxyadenosine (CdA) is a new drug for the treatment of ha iry cell leukemia and other lymphoproliferative diseases. It is genera lly administered as a continuous intravenous infusion during 5-7 days. The oral bioavailability is only 50%. The bioavailability after recta l administration was investigated in two patients with chronic lymphoc ytic leukemia. Five milligrams per square metre was given i.v, as a 2- h infusion and 24 h later the same dose was administered rectally in a gel formulation. The mean bioavailability was only 21% due to deglyco sylation of CdA to 2-chloroadenine (CAde. To further elucidate the fac tors which are important for the rectal availability of CdA, the in vi tro stability of CdA in bacterial cultures was tested. Clostridium per fringens and Escherichia coli as well as whole feces rapidly deglycosy lated CdA to CAde while Bacteroides fragilis, Enterococcus faecalis as well as saliva only degraded CdA slowly or not at all. It is conclude d that, due to bacterial degradation, rectal administration of CdA has no advantage over oral administration.