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. 1988 Feb;57(2):186–189. doi: 10.1038/bjc.1988.39

Pharmacokinetics and pharmacodynamics of locoregional 5 fluorouracil (5FU) in advanced colorectal liver metastases.

J A Goldberg 1, D J Kerr 1, N Willmott 1, J H McKillop 1, C S McArdle 1
PMCID: PMC2246442  PMID: 3358909

Abstract

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.

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Selected References

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  1. Au J. L., Rustum Y. M., Ledesma E. J., Mittelman A., Creaven P. J. Clinical pharmacological studies of concurrent infusion of 5-fluorouracil and thymidine in treatment of colorectal carcinomas. Cancer Res. 1982 Jul;42(7):2930–2937. [PubMed] [Google Scholar]
  2. Collins J. M., Dedrick R. L., King F. G., Speyer J. L., Myers C. E. Nonlinear pharmacokinetic models for 5-fluorouracil in man: intravenous and intraperitoneal routes. Clin Pharmacol Ther. 1980 Aug;28(2):235–246. doi: 10.1038/clpt.1980.156. [DOI] [PubMed] [Google Scholar]
  3. Dedrick R. L., Myers C. E., Bungay P. M., DeVita V. T., Jr Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep. 1978 Jan;62(1):1–11. [PubMed] [Google Scholar]
  4. Ensminger W. D., Gyves J. W., Stetson P., Walker-Andrews S. Phase I study of hepatic arterial degradable starch microspheres and mitomycin. Cancer Res. 1985 Sep;45(9):4464–4467. [PubMed] [Google Scholar]
  5. Ensminger W. D., Rosowsky A., Raso V., Levin D. C., Glode M., Come S., Steele G., Frei E., 3rd A clinical-pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2'-deoxyuridine and 5-fluorouracil. Cancer Res. 1978 Nov;38(11 Pt 1):3784–3792. [PubMed] [Google Scholar]
  6. Lee T. K., Sokoloski T. D., Royer G. P. Serum albumin beads: an injectable, biodegradable system for the sustained release of drugs. Science. 1981 Jul 10;213(4504):233–235. doi: 10.1126/science.6787705. [DOI] [PubMed] [Google Scholar]
  7. Powis G. Anticancer drug pharmacodynamics. Cancer Chemother Pharmacol. 1985;14(3):177–183. doi: 10.1007/BF00258112. [DOI] [PubMed] [Google Scholar]
  8. Sasaki Y., Imaoka S., Hasegawa Y., Nakano S., Ishikawa O., Ohigashi H., Taniguchi K., Koyama H., Iwanaga T., Terasawa T. Changes in distribution of hepatic blood flow induced by intra-arterial infusion of angiotensin II in human hepatic cancer. Cancer. 1985 Jan 15;55(2):311–316. doi: 10.1002/1097-0142(19850115)55:2<311::aid-cncr2820550202>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  9. Taylor I. Colorectal liver metastases--to treat or not to treat? Br J Surg. 1985 Jul;72(7):511–516. doi: 10.1002/bjs.1800720703. [DOI] [PubMed] [Google Scholar]
  10. Wagner J. G., Gyves J. W., Stetson P. L., Walker-Andrews S. C., Wollner I. S., Cochran M. K., Ensminger W. D. Steady-state nonlinear pharmacokinetics of 5-fluorouracil during hepatic arterial and intravenous infusions in cancer patients. Cancer Res. 1986 Mar;46(3):1499–1506. [PubMed] [Google Scholar]
  11. Weber G., Queener S. F., Ferdinandus J. A. Control of gene expression in carbohydrate, pyrimidine and DNA metabolism. Adv Enzyme Regul. 1970;9:63–95. doi: 10.1016/s0065-2571(71)80038-9. [DOI] [PubMed] [Google Scholar]
  12. Willmott N., Cummings J., Stuart J. F., Florence A. T. Adriamycin-loaded albumin microspheres: preparation, in vivo distribution and release in the rat. Biopharm Drug Dispos. 1985 Jan-Mar;6(1):91–104. doi: 10.1002/bdd.2510060111. [DOI] [PubMed] [Google Scholar]

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