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Pharmacokinetic Analysis of (6S)-5-Formyltetrahydrofolate (1-CF), (6R)-5-Formyltetrahydrofolate (d-CF) and 5-Methyltetrahydrofolate (5-CH3-THF) in Patients Receiving Constant i.v. Infusion of High-Dose (6R,S)-5-Formyltetrahydrofolate (Leucovorin)

  • J. A. Straw
  • E. M. Newman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 131)

Abstract

The biochemical rationale for the combination of leucovorin and fluorouracil presumes that administration of large doses of leucovorin will increase the endogenous pools of active folates and enhance the formation and/or stability of the thymidylate synthase-FdUMP-methylenetetrahydrofolate complex (1). A knowledge of the pharmacokinetic behavior of leucovorin and its active metabolite is essential if one is to select doses of leucovorin which will produce adequate plasma levels of active folates.

Keywords

Plasma Clearance Constant Infusion Pharmacokinetic Behavior Tetrabutylammonium Hydroxide Nonrenal Clearance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Moran, R.G. and Keyomarsi, K. Biochemical Rationale for the Synergism of 5-Fluorouracil and Folinic Acid. NCI Monographs No. 5: 159–162, 1987.PubMedGoogle Scholar
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    Blakley, R.L. The Biochemistry of Folic Acid and Related Pteridines, p. 82. New York: American Elsevier Publising Co., 1969.Google Scholar
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    Straw, J.A., Szapary, D., and Wynn W.T. Pharmacokinetics of the Diastereoisomers of Leucovorin after Intravenous and Oral Administration to Normal Subjects. Cancer Res. 44: 3114–3119, 1984PubMedGoogle Scholar
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    Newman, E.M. and Tsai, J.F. Microbiological Analysis of 5-Formyltetrahydrofolic Acid and Other Folates Using an Automatic 96-Well Plate Reader.Analytical Biochem. 154: 509–515, 1986.Google Scholar
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    Straw, J.A., Newman E.M., and J.H. Doroshow Pharmacokinetics of Leucovorin (d,1,-5-Formyltetrahydrofolate) After Intravenous Injection and Constant Intravenous Infusion. NCI Monographs No. 5: 41–45, 1987.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • J. A. Straw
    • 1
  • E. M. Newman
    • 2
  1. 1.Department of PharmacologyGeorge Washington UniversityWashingtonUSA
  2. 2.Division of PediatricsCity of Hope National Medical CenterDuarteUSA

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