Bioavailability and feasibility of subcutaneous 5-fluorouracil

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Abstract
Continuous intravenous (i.v.) infusion of 5-fluorouracil (5-FU) has been shown to be superior to bolus regimens in terms of response rates and toxicity. However, a continuous infusion is more expensive and prone to complications such as thromboembolism and infections. A way to circumvent these problems would be to administer 5-FU subcutaneously (s.c.). To assess feasibility and bioavailability of s.c. 5-FU, eight patients with advanced cancer received 250 mg 5-FU as an infusion over 90 min either intravenously (i.v.) or s.c. into the abdominal wall. The mean +/- s.d. bioavailability of s.c. 5-FU was 0.89 +/- 0.23. The interpatient variability for the area under the plasma concentration-time curve was 48% for the s.c. and 36% for the i.v. infusion. No local side effects were observed. To test the local tolerance of a more prolonged administration three patients received 930-1,000 mg m-2 5-FU by 24-h continuous s.c. infusion. The steady-state plasma levels were comparable to i.v. infusion. One patient developed a painless skin pigmentation at the s.c. infusion site. However, the same reaction was observed at the forearm after i.v. infusion. We conclude that at the dose studied s.c. 5-FU has an almost complete bioavailability and is well tolerated. Further work will show, whether prolonged s.c. infusion can be used as a safe and economical alternative to i.v. infusion.