Research in Experimental Medicine

, Volume 183, Issue 3, pp 167–175 | Cite as

Hepatic pharmacokinetics of glutaraldehyde-treated methotrexate-loaded carrier erythrocytes in dogs

  • J. R. DeLoach
  • C. H. Tangner
  • C. Barton
Original Papers


Methotrexate-loaded glutaraldehyde-treated canine carrier erythrocytes were used to deliver a 1.6-mg/kg dosage of drug. About 90% of the drug-loaded cells disappeared from circulation within 1 h. Approximately 11 mg of drug reached the liver, and a substantial portion of the methotrexate entered the enterohepatic bile salt circulation. Biochemical tests of liver function, such as alkaline phosphatase and serum glutamine pyruvate transaminase, indicated mild hepatocellular necrosis which was attributed to the action of methotrexate on the hepatocytes. Bilirubin levels were unchanged during and following drug treatment. The plasma half-life of the drug was extended 2.4-fold in the first 24 h following injection.

Key words

Glutaraldehyde Methotrexate Carrier erythrocytes Dog 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Beutler E, Dale GL, Guinto E, Kuhl N (1977) Enzyme replacement therapy in Gaucher's disease: Preliminary clinical trial of a new enzyme preparation. Proc Natl Acad Sci USA 74:4620–4623PubMedGoogle Scholar
  2. 2.
    Dale G, Villacorte DG, Beutler E (1977) High-yield entrapment of proteins into erythrocytes. Biochem Med 18:220–225CrossRefPubMedGoogle Scholar
  3. 3.
    DeLoach JR, Ihler GM (1977) A dialysis procedure for loading erythrocytes with enzymes and lipids. Biochim Biophys Acta 496:136–145PubMedGoogle Scholar
  4. 4.
    DeLoach JR, Peters S, Pinkard O, Glew R, Ihler G (1977) Effect of glutaraldehyde treatment on enzyme-loaded erythrocytes. Biochim Biophys Acta 496:507–515PubMedGoogle Scholar
  5. 5.
    DeLoach JR, Harris RL, Ihler GM (1980) An erythrocyte encapsular dialyzer used in preparing large quantities of erythrocyte ghosts and encapsulation of a pesticide in erythrocyte ghosts. Anal Biochem 102:220–227PubMedGoogle Scholar
  6. 6.
    DeLoach JR, Barton C (1981) Glutaraldehyde-treated carrier erythrocytes for organ targeting of methotrexate in dogs. Am J Vet Res 42:1971–1974PubMedGoogle Scholar
  7. 7.
    DeLoach JR, Barton C, Culler K (1981) Preparation of resealed carrier erythrocytes and in vivo survival in dogs. Am J Vet Res 42:667–669PubMedGoogle Scholar
  8. 8.
    Duke HH (1934) The physiology of domestic animals. Edward Brothers, Ann Arbor, MIGoogle Scholar
  9. 9.
    Henderson ES, Adamson RH, Denham C, Olivero VT (1965) The metabolic fate of triated methotrexate. I. Absorption, exretion, and distribution in mice, rats, dogs, and monkeys. Cancer Res 25:1008–1017PubMedGoogle Scholar
  10. 10.
    Hers P (1977) Principles of cancer chemotherapy. Vet Clin North Am 7:21–33PubMedGoogle Scholar
  11. 11.
    Morelli A, Benatti U, Salamino F, Sparatore B, Michette M, Melloni E, Pontremoli S, DeFlora A (1979) In vitro correction of erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. Arch Biochem Biophys 197:543–550PubMedGoogle Scholar
  12. 12.
    Rubin GJ, Jones BD (1981) The liver in pathophysiology in small animal surgery, 1st edn. Lea and Febiger, PhiladelphiaGoogle Scholar
  13. 13.
    Sprandel U, Hubbard AR, Chalmers RA (1979) In vitro studies on resealed erythrocyte ghosts as protein carriers. Res Exp Med 175:239–245Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • J. R. DeLoach
    • 1
    • 3
  • C. H. Tangner
    • 2
  • C. Barton
    • 2
  1. 1.US Department of AgricultureUS Livestock Insects Lab.KerrvilleUSA
  2. 2.Small Animal Medicine and Surgery, College of Veterinary MedicineTexas A M UniversityCollege StationUSA
  3. 3.Veterinary Toxicology and Entomology Research LaboratoryCollege StationUSA

Personalised recommendations