Intestinal absorption and first-pass elimination of 2', 3'-dideoxynucleosides following oral administration in rats.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Intestinal absorption and first-pass elimination of 2', 3'-dideoxynucleosides following oral administration in rats.

Biol Pharm Bull. 1996 Apr;19(4):599-603. Unique Identifier : AIDSLINE MED/97014131
Hasegawa T; Juni K; Saneyoshi M; Kawaguchi T; Faculty of Pharmaceutical Sciences, Josai University, Japan.

Abstract: Intestinal absorption and first-pass elimination of 2',3'-dideoxynucleosides (ddNs), including 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (DDI) and 2',3'-didehydro-3'-deoxythymidine (D4T), following oral administration was investigated in rats. Enzymatic degradation of ddNs in rat intestinal washing and in the intestinal homogenate showed them to be stable in the washing with half lives of more than 140 h, whereas degradation of DDI in the intestinal homogenate was more than ten times as rapid as those of AZT and D4T. Intestinal absorption was studied in three segments of the rat intestine (duodenum, jejunum and colon) using an in situ closed-loop method. The area under plasma ddN concentration curve AUC) and the residual percent of dose 1 h after dosing indicated a greater absorption of AZT and D4T in the upper intestinal tract than in the colon, very poor absorption of DDI in all segments, and considerable absorption of AZT in the colon. The AUC and the mean residence time (MRT) of ddNs following four different routes intravenous: i.v., intra portal vein: i.p.v., intra duodenal: i.d. and intra gastric: i.g.) were measured using the in viva multiple sites of input method in rats. AZT and D4T were rapidly absorbed from the gastrointestinal tract and their bioavailability was more than 90%. DDI was less absorbed (33.02%) following i.d. administration compared with AZT and D4T. This poor absorption of DDI was partly attributable to its metabolism in the intestine.

Keywords: *Intestines/METABOLISM
970730
M9772130

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