A pharmacokinetic comparison of intravenous versus intra-arterial folinic acid.
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 micrograms ml-1 h-1 (SD 41), 18.5 micrograms ml-1 (SD 1.2) and 7.41 m-2 (SD 0.44) respectively following intravenous administration of folinic acid compared with 142 micrograms ml-1 h-1 (SD 45), 14.8 micrograms ml-1 (SD 2.4) and 11.21 m-2 (SD 1.22) following intra-hepatic arterial administration (P less than 0.05). Regional folinic acid was therefore associated with a statistically significant reduction in systemic exposure compared with the intravenous route.
Anderson
J H
JH
University Department of Surgery, Royal Infirmary, Glasgow, UK.
Kerr
D J
DJ
Setanoians
A
A
Cooke
T G
TG
McArdle
C S
CS
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D012004:Rectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery
D002955:Leucovorin; D005472:Fluorouracil