Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 1995 Aug;12(8):1158-64.
doi: 10.1023/a:1016259826037.

Species dependent esterase activities for hydrolysis of an anti-HIV prodrug glycovir and bioavailability of active SC-48334

C S Cook  1 , P J Karabatsos, G L Schoenhard, A Karim
Affiliations
Clinical Trial

Species dependent esterase activities for hydrolysis of an anti-HIV prodrug glycovir and bioavailability of active SC-48334

C S Cook et al. Pharm Res. 1995 Aug.

Abstract

Purpose: The in vitro fate of an ester prodrug, glycovir, was studied to determine if the species differences in the bioavailability of pharmacologically active SC-48334 observed after glycovir administration and not observed after SC-48334 administration is due to species differences in ester hydrolysis rate or species differences in absorption of the prodrug itself, and to determine the site(s) of ester hydrolysis which contributes most to species differences in the bioavailability of SC-48334 if any.

Methods: Glycovir was incubated with small intestinal mucosa, liver S9 fractions, whole blood, red blood cells (RBC) and plasma of the rat, dog, monkey (cynomolgus and rhesus) and man, and glycovir concentrations were determined by HPLC.

Results: The relative bioavailabilities of SC-48334 after prodrug administration to the rat, dog, monkey and man were 99, 15, 42 and 37%, respectively. After SC-48334 administration, SC-48334 was rapidly and similarly well absorbed in all species. The hydrolysis rate in the small intestinal mucosa was well correlated with the relative bioavailability of SC-48334 after prodrug administration. Among different species the hydrolysis rate of glycovir in liver S9 fractions, blood, RBC and plasma did not parallel those in the mucosa of the small intestine.

Conclusions: The species differences in bioavailability of SC-48334 with the prodrug were due to species differences in hydrolysis rates of the prodrug in small intestinal mucosa. The monkey was a good animal model for prediction of esterase activity in human small intestine and relative bioavailability in man.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Pharm Sci. 1972 Mar;61(3):379-85 - PubMed
    1. Chem Pharm Bull (Tokyo). 1989 Dec;37(12):3272-6 - PubMed
    1. Biochem J. 1953 Jan;53(1):110-7 - PubMed
    1. Fundam Appl Toxicol. 1988 Aug;11(2):323-32 - PubMed
    1. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9229-33 - PubMed

MeSH terms

LinkOut - more resources