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Pharmacokinetics of high-dose methotrexate in dogs

An experimental model with diffusion chambers

  • Original Articles
  • Methotrexate, Tissue Concentrations
  • Published:
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Summary

The usefulness of a diffusion chamber method for determination of concentrations of cytostatic drugs in the interstitial fluid of tissues was tested. Chambers with a permeable membrane (pore size: 0.45 μm) were implanted in the liver, kidney, bladder wall, and prostate of dogs. After administration of high doses of methotrexate (100 mg/kg body wt) the concentrations in the chamber fluid and in serum were measured simultaneously and repeatedly for 72 h.

The method proved to be effective for collecting data on the distribution of drugs in different organs. The results show that knowledge of the serum concentration does not permit predictions of the drug concentration in the interstitial fluid of various tissues to be made.

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References

  1. Bergan T (1981) Pharmacokinetics of tissue penetration of antibiotics. Rev Infect Dis 3:45

    Google Scholar 

  2. Berkowitz RS, Goldstein DP, Jones MA, Marean AR, Bernstein MR (1980) Methotrexate with cirtrovorum factor rescue reduced chemotherapy toxicity in the management of gestational trophoblastic neoplasms. Cancer 45:423

    Google Scholar 

  3. Chabner BA, Slavik M (1975) Perspectives on high-dose methotrexate (NSC-740) therapy. Cancer Chemother Rep 6:1

    Google Scholar 

  4. Chen HSG, Gross JF (1979) Physiologically based pharmacokinetic models for anticancer drugs. Cancer Chemother Pharmacol 2:85

    Google Scholar 

  5. Chisholm GD (1978) The tissue cage model in the distribution of antibacterial agents. Scand J Infect Dis [Suppl] 14:118

    Google Scholar 

  6. De Kernion JB (1977) The chemotherapy of advanced bladder carcinoma. Cancer Res 37:2771

    Google Scholar 

  7. Djerassi I (1975) Hig-dose methotrexate (NSC-740) and citrovorum factor (NSC-3590) rescue: Background and rationale. Cancer Chemother Rep 6:3

    Google Scholar 

  8. Frei E, Blum RH, Pitman SW, Kirkwood JM, Craic-Henderson I, Skarin AT, Mayer RJ, Bast RC, Garnick MB, Parker LM, Canellos GP (1980) High-dose methotrexate with leucovorin rescue: Rationale and spectrum of antitumor activity. Am J Med 68:37

    Google Scholar 

  9. Georgopoulos A, Schütze E, Laber G (1980) Measurements of antimicrobial drug concentrations in renal interstitial fluid using the diffusion chamber technique. Infection 8:115

    Google Scholar 

  10. Goh TS, Wong KY, Lampkin B, O'Leary J, Gnarra D (1979) Evaluation of 24-hour infusion of high-dose methotrexate—Pharmacokinetics and toxicity. Cancer Chemother Pharmacol 3:177

    Google Scholar 

  11. Gomeni C, Gomeni R (1978) GPHARM, an interactive graphic package for pharmacokinetic analysis. Comp Biomed Res 11:345

    Google Scholar 

  12. Jacobi GH (1979) Stellenwert der systemischen Chemotherapie beim fortgeschrittenen Harnblasenkarzinom. In: Jakobi GH, Altwein JE (Hrsg) Chemotherapie urologischer Malignome. Karger, Basel, S 141

    Google Scholar 

  13. Jain RK, Wei J, Gullino PM (1979) Pharmacokinetics of methotrexate in solid tumors. J Pharmacokinet Biopharm 7:181

    Google Scholar 

  14. Laber G, Schütze E, Leskova R, Kolb R, Georgopoulos A (1980) A diffusion chamber technique for measuring concentrations of antibiotics in interstitial fluid. Infection 8:58

    Google Scholar 

  15. Lenzhofer R, Jaschek I, Breyer St, Graininger W, Moser K (1979) Ergebnisse und pharmakokinetische Untersuchungen bei hochdosierter Methotrexat-Therapie. Acta Med Austriaca 6:331

    Google Scholar 

  16. Martin BK (1967) Drug urinary excretion data — Some aspects concerning the interpretation. Br J Pharmacol Chemother 29:191

    Google Scholar 

  17. Possinger K, Hartenstein R, Ehrhart H (1981) Chemotherapie des Adenokarzinoms der Niere. In: Rattenhuber U, Wieland W, (Hrsg) Diagnostik and Therapie des Nierenkarzinoms. Zuckschwerdt, München, S 183

    Google Scholar 

  18. Pratt CB, Roberts D, Shanks E, Warmath EL (1975) Response, toxicity, and pharmacokinetics of high-dose methotrexate (NSC-740) with citrovorum factor (NSC-3590) rescue for children with osteosarcoma and other malignant tumors. Cancer Chemother Rep 6:13

    Google Scholar 

  19. Schmook FP, Nefzger M, Laber G, Georgopoulos A, Czok R, Schütze E (1980) Composition of fluids from diffusion chambers implanted in the soft tissue and kidneys of rabbits. Infection 8:156

    Google Scholar 

  20. Snedecor GW, Cochran WG (1967) Statistical methods, 6th edn. Iowa State University Press, Iowa

    Google Scholar 

  21. Stoller RG, Jacobs SA, Drake JC, Lutz RJ, Chabner BA (1975) Pharmacokinetics of high-dose methotrexate (NSC-740). Cancer Chemother Rep 6:19

    Google Scholar 

  22. Van den Berg HW, Murphy RF, Kennedy DG (1980) Rapid plasma clearance and reduced rate and extent of urinary elimination of parenterally administered methotrexate as a result of severe vomiting and diarrhoea. Cancer Chemother Pharmacol 4:47

    Google Scholar 

  23. Virtanen R, Iisalo E, Parvinen M, Nordman E (1979) Methotrexate concentrations in biological fluids: Comparison of results obtained by radioimmunoassay and direct ligand binding radioassay. Acta Pharmacol Toxicol 44:296

    Google Scholar 

  24. Yagoda A (1980) Chemotherapy of metastatic bladder cancer. Cancer 45:1879

    Google Scholar 

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Porpaczy, P., Schmidbauer, C.P., Georgopoulos, A. et al. Pharmacokinetics of high-dose methotrexate in dogs. Cancer Chemother. Pharmacol. 11, 172–176 (1983). https://doi.org/10.1007/BF00254199

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  • DOI: https://doi.org/10.1007/BF00254199

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