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

Sharma, Ricky A., Eatock, Martin M., Twelves, Christopher J., Brown, Gill, McLelland, Heather R., Clayton, Kathryn T., O'Byrne, Kenneth J., Moyses, Chris, Carmichael, James, & Steward, William P. (2001) Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver. Cancer Chemotherapy and Pharmacology, 48(3), pp. 197-201.

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Purpose: Although oral fluoropyrimidine pro-drugs 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/m 2) 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.

Impact and interest:

2 citations in Scopus
2 citations in Web of Science®
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ID Code: 65681
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: 5-Fluorouracil, Carcinoma, Chemotherapy, Pharmacokinetics, 1 galactopyranosyl 5 fluorouracil, fluorouracil, nucleoside analog, ogt 719, unclassified drug, adult, aged, article, bioavailability, cancer chemotherapy, clinical article, clinical trial, crossover procedure, cytotoxicity, diarrhea, dose response, drug efficacy, drug half life, drug tolerability, female, gastrointestinal symptom, hepatoma cell, human, liver function, liver metabolism, liver tumor, malaise, male, neutropenia, pneumonia, priority journal, survival time, thrombocyte count, thrombocytopenia, Administration, Oral, Antineoplastic Agents, Area Under Curve, Biological Availability, Drug Administration Schedule, Fluoresceins, Humans, Infusions, Intravenous, Liver, Maximum Tolerated Dose, Metabolic Clearance Rate, Middle Aged, Neoplasms, Treatment Outcome
DOI: 10.1007/s002800100332
ISSN: 0344-5704
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2001 Springer
Deposited On: 06 Jan 2014 04:35
Last Modified: 24 Jun 2017 14:36

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