Skip to main content
SpringerLink
Log in

Pharmacokinetic study of fludarabine phosphate (NSC 312887)

  • Original Articles
  • Pharmacokinetics, Fludarabine
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

Characterization of the pharmacokinetics of 2-FLAA has been completed in seven patients receiving 18 or 25 mg/m2 daily x5 of 2-FLAMP over 30 min. Assuming 2-FLAMP was instantaneously converted to 2-FLAA, the plasma levels of 2-FLAA declined in a biexponential fashion. Computer fitting of the plasma concentrationtime curves yielded an average distribution half-life (t1/2α) of 0.60 h and a terminal half-life (t1/2β) of 9.3 h. The estimated plasma clearance was 9.07±3.77 l/h per m2 and the steady state volume of distribution, 96.2±26.0 l/m2. There was a significant inverse correlation between the area under the curve (AUC) and absolute granulocyte count (r=-0.94, P<0.02). A relationship between creatinine clearance and total body clearance was noted, but was not statistically significant (r=0.828; P<0.1). Aproximately 24%±3% of 2-FLAA was excreted renally over the 5-day course of drug administration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

2-FLAA-9-β-D:

arabinofuranosyl-2-fluoroadenine

2-FLAMP:

the 5'-monophosphate of 2-FLAA, also known as fludarabine phosphate

AUC:

area under the curve

AGC:

absolute granulocyte count

TPC:

total plasma clearance

Vdss :

volume of distribution at steady state

Vd:

volume of distribution

Creat Cl:

creatinine clearance

SGOT:

serum glutamic-oxaloacetic transaminase

WBC:

peripheral white blood cell count

References

  1. Avramis VI, Plunkett W (1983) 2-Fluoro-ATP: A toxic metabolite of 9-β-D-arabinosyl-2-fluoroadenine. Biochem Biophys Res Commun 113: 35–43

    Google Scholar 

  2. Boxenbaum HG, Riegelman S, Elashoff RM (1974) Statistical estimations in pharmacokinetics. J Pharmacokin Biopharm 2: 123–148

    Google Scholar 

  3. Brockman RW, Schabel FM Jr, Montgomery JA (1977) Biologic activity of 9-β-D-arabinofuranosyl-2-fluoroadenine, a metabolically stable analog of 9-β-D-arabinofuranosyladenine. Biochem Pharmacol 26: 2193–2196

    Google Scholar 

  4. Brockman RW, Cheng Y-C, Schabel FM Jr, Montgomery JA (1980) Metabolism and chemotherapeutic activity of 9-β-D-arabinofuranosyl-2-fluoroadenine against murine leukemia L1210 and evidence of its phosphorylation by deoxycytidine kinase. Cancer Res 40: 3610–3615

    Google Scholar 

  5. Hutton JJ, Von Hoff D, Kuhn J, Phillips J, Hersh M, Clark G (1984) Phase I clinical investigation of 9-β-D-arabinofuranosyl-2-fluoroadenine-5′-monophosphate (NSC 312887), a new purine antimetabolite. Cancer Res 44: 4183–4186

    Google Scholar 

  6. Jusko W (1980) Guidelines for collection and pharmacokinetic analysis of drug disposition data. In Evans WE, Schentag JJ, Jusko WJ: Applied pharmacokinetics. Applied Therapeutics, San Francisco, pp 639–680

    Google Scholar 

  7. Malspeis L, De Souza JJV, Staubus AE, Neidhart JA, Grever MR (1984) Pharmacokinetics of 2-F-Ara-AMP in man during a phase I clinical trial. Investigat New Drugs 2: 116

    Google Scholar 

  8. Metzler CM, Elfring GL, McEwen AJ (1976) A users' manual: NONLIN and associated programs, Upjohn, Kalamazoo

    Google Scholar 

  9. Noker PE, Duncan GF, El Dareer SM, Hill DL (1983) Disposition of 9-β-D-arabinofuranosyl-2-fluoroadenine 5′-phosphate in mice and dogs. Cancer Treat Rep 67: 445–446

    Google Scholar 

  10. Plunkett W, Chubb S, Alexander L, Montgomery JA (1980) Comparison of the toxicity and metabolism of 9-β-D-arabinofuranosyl-2-fluoroadenine and 9-β-D-arabinofuranosyladenine in human lymphoblastoid cells. Cancer Res 40: 2349–2355

    Google Scholar 

  11. Von Hoff DD, Coltman CA, Forseth B (1981) Activity of mitoxantrone in a human tumor cloning system. Cancer Res 41: 1853–55

    Google Scholar 

  12. Yamaoka K, Nakagawa T, Uno T (1978) Application of Akaike's information criterion (AIC) in evaluation of linear pharmacokinetic equations. J Pharmacokin Biopharm 6: 165–175

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmacy, University of Texas Health Science Center at San Antonio, 78284, San Antonio, TX, USA

    Marla R. Hersh, John G. Kuhn & Thomas M. Ludden

  2. Audie L. Murphy Memorial Veterans Hospital, 78284, San Antonio, TX, USA

    Jerry L. Phillips

  3. the Cancer Therapy and Research Center, 78284, San Antonio, TX, USA

    Jerry L. Phillips

  4. Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, 78284, San Antonio, TX, USA

    Marla R. Hersh, John G. Kuhn, Jerry L. Phillips, Gary Clark, Thomas M. Ludden & Daniel D. Von Hoff

Authors
  1. Marla R. Hersh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John G. Kuhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jerry L. Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gary Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas M. Ludden
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniel D. Von Hoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This study was supported by contract NCI N01-CM-27542, NIH grant RR-01346 and by the VA Research Service.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hersh, M.R., Kuhn, J.G., Phillips, J.L. et al. Pharmacokinetic study of fludarabine phosphate (NSC 312887). Cancer Chemother. Pharmacol. 17, 277–280 (1986). https://doi.org/10.1007/BF00256699

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00256699

Keywords

Search

Navigation