Pharmacokinetics and pharmacodynamics of locoregional 5 fluorouracil (5FU) in advanced colorectal liver metastases

By measuring peripheral drug levels in plasma, the effect of combining albumin microspheres with angiotensin II on systemic exposure to 5FU when administered by bolus injection into the hepatic artery in patients with advanced colorectal liver metastases has been assessed. The results suggest that d...

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Bibliographic Details
Published in:British journal of cancer 1988-02, Vol.57 (2), p.186-189
Main Authors: GOLDBERG, J. A, KERR, D. J, WILLMOTT, N, MCKILLOP, J. H, MCARDLE, C. S
Format: Article
Language:English
Subjects:
Albumins - administration & dosage
Angiotensin II - administration & dosage
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Colonic Neoplasms - blood
Fluorouracil - administration & dosage
Fluorouracil - blood
Fluorouracil - pharmacokinetics
Hepatic Artery
Humans
Injections, Intra-Arterial
Leukocyte Count
Liver Neoplasms - blood
Liver Neoplasms - drug therapy
Liver Neoplasms - secondary
Medical sciences
Microspheres
Pharmacology. Drug treatments
Platelet Count
Rectal Neoplasms - blood
Time Factors
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Summary:By measuring peripheral drug levels in plasma, the effect of combining albumin microspheres with angiotensin II on systemic exposure to 5FU when administered by bolus injection into the hepatic artery in patients with advanced colorectal liver metastases has been assessed. The results suggest that despite hepatic arterial administration of 5FU, there was no reduction in systemic exposure when compared with that associated with intravenous injection of the same dose. Neither albumin microspheres nor angiotensin II appeared to improve the regional advantage. There have been a number of reports relating the plasma levels of cytotoxic agents with pharmacodynamic parameters. We have shown significant direct correlations between 5FU clearance and 1 week post treatment platelet and white cell counts, and an inverse relationship between the area under the 5FU plasma concentration-time curve (AUC) and 1 week post treatment platelet count and white cell count respectively.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1988.39