Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1979 Jun;7(6):613–617. doi: 10.1111/j.1365-2125.1979.tb04651.x

Plasma levels of 5-fluorouracil after oral and intravenous administration in cancer patients.

R E Finch, M R Bending, A F Lant
PMCID: PMC1429669  PMID: 465283

Abstract

1. Plasma levels of 5-fluorouracil (5FU) have been determined in eleven cancer patients after 0.5 g and 1.0 g intravenous doses, and in one patient after paired 1.0 g oral and intravenous doses. 2. The plasma half-life after the 0.5 g intravenous dose was relatively constant, irrespective of the stage and spread of the disease. 3. Plasma kinetics of the drug were dose dependent. Doubling of the intravenous dose produced a 1.5-fold increase in plasma half life, a two-fold increase in initial plasma drug concentration, and a three-fold increase in area under the concentration/time curve. 4. In one patient receiving paired 1.0 g intravenous and oral doses nine weeks apart, an increase in the bioavailability of the drug coincided with a marked clinical regression in palpable intra-abdominal metastases. 5. The significance of measuring plasma drug kinetics and their relationship to drug efficacy and toxicity are discussed.

Full text

PDF
613

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ANSFIELD F. J. A LESS TOXIC FLUOROURACIL DOSAGE SCHEDULE. JAMA. 1964 Nov 16;190:686–688. doi: 10.1001/jama.1964.03070200122030. [DOI] [PubMed] [Google Scholar]
  2. Barza M., Lauermann M. Why monitor serum levels of gentamicin? Clin Pharmacokinet. 1978 May-Jun;3(3):202–215. doi: 10.2165/00003088-197803030-00002. [DOI] [PubMed] [Google Scholar]
  3. Bender R. A., Zwelling L. A., Doroshow J. H., Locker G. Y., Hande K. R., Murinson D. S., Cohen M., Myers C. E., Chabner B. A. Antineoplastic drugs: clinical pharmacology and therapeutic use. Drugs. 1978 Jul;16(1):46–87. doi: 10.2165/00003495-197816010-00003. [DOI] [PubMed] [Google Scholar]
  4. Bruckner H. W., Creasey W. A. The administration of 5-fluorouracil by mouth. Cancer. 1974 Jan;33(1):14–18. doi: 10.1002/1097-0142(197401)33:1<14::aid-cncr2820330106>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  5. Chabner B. A., Myers C. E., Oliverio V. T. Clinical pharmacology of anticancer drugs. Semin Oncol. 1977 Jun;4(2):165–191. [PubMed] [Google Scholar]
  6. Chadwick M., Rogers W. I. The physiological disposition of 5-fluorouracil in mice bearing solid L1210 lymphocytic leukemia. Cancer Res. 1972 May;32(5):1045–1056. [PubMed] [Google Scholar]
  7. Chirstophidis N., Vajda F. J., Lucas I., Drummer O., Moon W. J., Louis W. J. Fluorouracil therapy in patients with carcinoma of the large bowel: a pharmacokinetic comparison of various rates and routes of administration. Clin Pharmacokinet. 1978 Jul-Aug;3(4):330–336. doi: 10.2165/00003088-197803040-00006. [DOI] [PubMed] [Google Scholar]
  8. Cohen J. L., Irwin L. E., Marshall G. J., Darvey H., Bateman J. R. Clinical pharmacology of oral and intravenous 5-fluorouracil (NSC-19893). Cancer Chemother Rep. 1974 Sep-Oct;58(5 Pt 1):723–731. [PubMed] [Google Scholar]
  9. Costanzi J. J., Coltman C. A., Jr Combination chemotherapy using cyclophosphamide, vincristine, methotrexate and 5-fluorouracil in solid tumors. Cancer. 1969 Mar;23(3):589–596. doi: 10.1002/1097-0142(196903)23:3<589::aid-cncr2820230310>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  10. Finch R. E., Bending M. R., Lant A. F. Use of a nitrogen detector for GLC determination of fluorouracil in plasma during single- and combined-agent chemotherapy. J Pharm Sci. 1978 Oct;67(10):1489–1490. doi: 10.1002/jps.2600671051. [DOI] [PubMed] [Google Scholar]
  11. Finj C., Sadée W. Determination of 5-fluorouracil (NSC-19893) plasma levels in rats and man by isotope dilution-mass fragmentography. Cancer Chemother Rep. 1975 Mar-Apr;59(2 Pt 1):279–286. [PubMed] [Google Scholar]
  12. Gardner M. L., Samson R. R., Heading R. C. Changes in absorptive and peptide hydrolase activities in rat small intestine after administration of 5-fluorouracil. Clin Sci Mol Med. 1978 Apr;54(4):411–418. doi: 10.1042/cs0540411. [DOI] [PubMed] [Google Scholar]
  13. Garrett E. R., Hurst G. H., Green J. R., Jr Kinetics and mechanisms of drug action of microorganisms XXIII: microbial kinetic assay for fluorouracil in biological fluids and its application to human pharmacokinetics. J Pharm Sci. 1977 Oct;66(10):1422–1429. doi: 10.1002/jps.2600661019. [DOI] [PubMed] [Google Scholar]
  14. HEIDELBERGER C., ANSFIELD F. J. EXPERIMENTAL AND CLINICAL USE OF FLUORINATED PYRIMIDINES IN CANCER CHEMOTHERAPY. Cancer Res. 1963 Sep;23:1226–1243. [PubMed] [Google Scholar]
  15. Hanham I. W., Newton K. A., Westbury G. Seventy-five cases of solid tumours treated by a modified quadruple chemotherapy regime. Br J Cancer. 1971 Sep;25(3):462–478. doi: 10.1038/bjc.1971.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jacobs E. M., Reeves W. J., Jr, Wood D. A., Pugh R., Braunwald J., Bateman J. R. Treatment of cancer with weekly intravenous 5-fluorouracil. Study by the Western Cooperative Cancer Chemotherapy Group (WCCCG). Cancer. 1971 Jun;27(6):1302–1305. doi: 10.1002/1097-0142(197106)27:6<1302::aid-cncr2820270604>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  17. Kaufman S. 5-Fluorouracil in the treatment of gastrointestinal neoplasia. N Engl J Med. 1973 Jan 25;288(4):199–201. doi: 10.1056/NEJM197301252880408. [DOI] [PubMed] [Google Scholar]
  18. Sadee W., Wong C. G. Pharmacokinetics of 5-fluorouracil: inter-relationship with biochemical kinetics in monitoring therapy. Clin Pharmacokinet. 1977 Nov-Dec;2(6):437–450. doi: 10.2165/00003088-197702060-00004. [DOI] [PubMed] [Google Scholar]
  19. Seifert P., Baker L. H., Reed M. L., Vaitkevicius V. K. Comparison of continuously infused 5-fluorouracil with bolus injection in treatment of patients with colorectal adenocarcinoma. Cancer. 1975 Jul;36(1):123–128. doi: 10.1002/1097-0142(197507)36:1<123::aid-cncr2820360108>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  20. Shane S. J., Iazzetta J. J., Chisholm A. W., Berka J. F., Leung D. Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man. Br J Clin Pharmacol. 1978 Jul;6(1):37–41. doi: 10.1111/j.1365-2125.1978.tb01679.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stoller R. G., Hande K. R., Jacobs S. A., Rosenberg S. A., Chabner B. A. Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity. N Engl J Med. 1977 Sep 22;297(12):630–634. doi: 10.1056/NEJM197709222971203. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES