Bioavailability and bacterial degradation of rectally administered 2-chloro-2'-deoxyadenosine.
2-Chloro-2'-deoxyadenosine (CdA) is a new drug for the treatment of hairy cell leukemia and other lymphoproliferative diseases. It is generally administered as a continuous intravenous infusion during 5-7 days. The oral bioavailability is only 50%. The bioavailability after rectal administration was investigated in two patients with chronic lymphocytic 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 deglycosylation of CdA to 2-chloroadenine (CAde). To further elucidate the factors which are important for the rectal availability of CdA, the in vitro stability of CdA in bacterial cultures was tested. Clostridium perfringens and Escherichia coli as well as whole feces rapidly deglycosylated CdA to CAde while Bacteroides fragilis, Enterococcus faecalis as well as saliva only degraded CdA slowly or not at all. It is concluded that, due to bacterial degradation, rectal administration of CdA has no advantage over oral administration.
Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
J
J
Liliemark
F
F
Albertioni
C
C
Edlund
G
G
Juliusson
D000285:Administration, Rectal; D000368:Aged; D001419:Bacteria / Q000378:metabolism*; D001682:Biological Availability; D001711:Biotransformation; D017338:Cladribine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism
D017338:Cladribine