Improvement of the oral bioavailability of naltrexone in dogs: a prodrug approach

In an effort to improve the oral bioavailability of naltrexone [17-(cyclopropylmethyl)-4,5 alpha-epoxy-3,14-dihydroxymorphinan-6-one;1], a number of prodrug esters on the 3-hydroxyl group were prepared: the anthranilate (2), acetylsalicylate (3), benzoate (4), and pivalate (5). The oral bioavailabil...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of pharmaceutical sciences Vol. 76; no. 5; p. 356
Main Authors:	Hussain, M A, Koval, C A, Myers, M J, Shami, E G, Shefter, E
Format:	Journal Article
Language:	English
Published:	United States 01-05-1987
Subjects:	Administration, Oral Animals Aspirin Benzoates Benzoic Acid Biological Availability Carboxylic Acids - metabolism Dogs Esters - metabolism Female Humans Hydrolysis Kinetics Naltrexone - administration & dosage Naltrexone - blood Naltrexone - metabolism ortho-Aminobenzoates Pentanoic Acids
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	In an effort to improve the oral bioavailability of naltrexone [17-(cyclopropylmethyl)-4,5 alpha-epoxy-3,14-dihydroxymorphinan-6-one;1], a number of prodrug esters on the 3-hydroxyl group were prepared: the anthranilate (2), acetylsalicylate (3), benzoate (4), and pivalate (5). The oral bioavailability of these prodrugs was determined in dogs. Compounds 2 and 3 exhibited the greatest enhancement of naltrexone bioavailability (45 and 28 times greater than 1, respectively). No correlation was found between the rates of plasma hydrolysis and bioavailability. Naltrexone-3-acetylsalicylate hydrolyzed in human and dog plasma with a fast deacetylation step to naltrexone salicylate followed by a slower hydrolysis step to naltrexone.
ISSN:	0022-3549
DOI:	10.1002/jps.2600760503