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Investigational New Drugs

, Volume 1, Issue 3, pp 219–224 | Cite as

Pharmacokinetic study of methyl glyoxal-bis-guanylhydrazone (methyl-GAG)

  • Milan Slavik
  • Thomas Clouse
  • Alan Wood
  • Oscar Blanc
  • Robert C. Eschbach
Preclinical

Summary

Using a paired ion exchange high pressure liquid Chromatographic assay, pharmacokinetic evaluation of methyl glyoxal bis guanylhydrazone (methyl-GAG) was performed in nine male New Zealand albino rabbits following administration of a single intravenous bolus dose of 50 mg/kg B.W (550 mg/m2 BSA).

Blood samples were collected before and at intervals of 5, 10, 15, 30 min and 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after administration of the drug.

The analysis of experimental data indicates a three compartment open model with first order elimination from the central compartment described by the equation C pt =A.e−αt+B.e−βt+C.e−γt, where A, B, C, are 107.985, 4.785, and 0.763 μg/ml, respectively, α, β,γ, are 5.466, 0.487, and 0.030 h−1, respectively, and \(T_{\frac{1}{2}\alpha ,\beta ,\gamma } \) are 7.6, 85.3 min and 23.1 h, respectively. The mean volume of distribution in the central compartment V c was 0.44 liters (l)/kg, volume of distribution Vd area 30.326 l/kg, and the total body clearance 0.9097 l/kg/h. The existence of a long terminal plasma half life of methyl-GAG reported previously in human studies was also confirmed in experimental animals and may explain the cumulative toxicity of this drug.

Key words

methyl-GAG rabbits pharmacokinetics three compartmental model 

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Copyright information

© Martinus Nijhoff Publishers 1983

Authors and Affiliations

  • Milan Slavik
    • 1
    • 2
    • 3
  • Thomas Clouse
    • 1
  • Alan Wood
    • 1
  • Oscar Blanc
    • 1
  • Robert C. Eschbach
    • 4
  1. 1.Laboratory of Clinical Pharmacology, Cancer Research and Treatment Center University of New Mexico, School of MedicineAlbuquerqueUSA
  2. 2.Department of MedicineUniversity of New Mexico, School of MedicineAlbuquerqueUSA
  3. 3.Department of PharmacologyUniversity of New Mexico, School of MedicineAlbuquerqueUSA
  4. 4.College of PharmacyAlbuquerqueUSA

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