A pharmacokinetic comparison of intravenous versus intra-arterial folinic acid

Abstract

Recent clinical trials have suggested that a combination of folinic acid and 5-fluorouracil (5-FU) may improve response rates and survival in patients with advanced colorectal cancer. However, this regimen has been complicated by potentially life threatening toxicity. Regional delivery of folinic acid via a hepatic artery catheter might be expected to reduce systemic exposure and subsequent adverse effects. The present study compared the pharmacokinetic profiles of intravenous and intra-hepatic arterial infusions of folinic acid in patients with colorectal liver metastases (n = 6) who were being treated with weekly regional infusions of 5-FU. The mean area under the plasma concentration - time curve, the peak plasma concentration and the steady state volume of distribution were 163 μg ml-1 h-1 (SD 41), 18. 5 μg ml-1 (SD 1. 2) and 7. 41 m-2 (SD 0. 44) respectively following intravenous administration of folinic acid compared with 142 μg ml-1h-1 (SD45), 14. 8 μg ml-1 (SD 2. 4) and 11. 21m-2 (SD 1. 22) following intra-hepatic arterial administration (P<0. 05). Regional folinic acid was therefore associated with a statistically significant reduction in systemic exposure compared with the intravenous route. © Macmillan Press Ltd., 1992.