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 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.