Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver.

Abstract:

PURPOSE:Although oral fluoropyrimidine prodrugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. METHOD:Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m2) OGT 719. RESULTS:Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. CONCLUSION:The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

authors

Sharma RA,Eatock MM,Twelves CJ,Brown G,McLelland HR,Clayton KT,O'Byrne KJ,Moyses C,Carmichael J,Steward WP

doi

10.1007/s002800100332

keywords:

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

197-201

issue

3

eissn

0344-5704

issn

1432-0843

journal_volume

48

pub_type

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