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  • 1985-1989  (2)
  • 1965-1969
  • 1955-1959
  • 1985  (2)
Material
Years
  • 1985-1989  (2)
  • 1965-1969
  • 1955-1959
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 13 (1985), S. 13-39 
    ISSN: 1573-8744
    Keywords: pharmacokinetics, physiologic model ; cis-dichlorodiammineplatinum(II) ; cis-platin ; DDP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A physiological model has been developed to describe the disposition of cisdichlorodiammine-platinum(II) (DDP) following i.v. dosing in the female rat bearing the Walker 256 carcinoma. The model simulates concentrations of DDP and its mobile and fixed metabolites in plasma, liver, gut, skin, muscle, tumor, carcass, and kidney, and DDP and mobile metabolite excretion following a 4 mg/kg dose. In the kinetic model, DDP binds irreversibly to low MW nucleophiles and macromolecules (largely proteins) within the plasma and tissue compartments to form mobile and fixed metabolites, respectively. Reaction rates for the formation of each metabolite are tissue/organ specific. The rate constant for the biotransformation of DDP to fixed metabolite in plasma (k 2p=0.0082 min−) was determined from in vitro incubation studies. This rate was used as the basis for estimating the biotransformation rate constants for DDP to fixed and mobile metabolites in other compartments. Both DDP and mobile metabolite are assumed to follow flowlimited transport, to freely traverse compartmental barriers, and to partition equally in all compartments. Both are excreted in the urine, the major route of Pt elimination. Urinary excretion is modeled as a linear process involving filtration only; an assumption based on a calculated renal clearance of 1.1 ml/min, a value very similar to the estimated GFR. Biliary excretion is a minor route of mobile metabolite elimination and is modeled as a linear process occurring in the liver. Four hours after dosing, approximately 60% of the administered Pt remains in the tissues and plasma. Of this, over 75% of the plasma Pt and 90% of the metal ion in every other compartment is fixed (protein bound). Fixed Pt can be eliminated from a compartment only after its biotransformation to mobile metabolite. In most compertments this rate of elimination corresponds closely to the average rate of protein turnover in that compartment.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Molecular genetics and genomics 201 (1985), S. 505-512 
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In mammals, a number of liver-derived plasma proteins, termed acute phase reactants, are induced during an inflammation response. We have studied genetic variation in the structure and expression of several of these proteins in a variety of inbred and wild-derived mice. In a genetic cross, electrophoretic polymorphisms for the two α1-acid glycoproteins, AGP-1 and AGP-2, co-segregated in 58 backcross progeny, indicating that either a single gene or two tightly-linked genes on chromosome 4 encode the AGPs. In the same backcross, segregation of variation in haptoglobin structure showed that the gene encoding this acute phase reactant is on chromosome 8. Structural variation in serum amyloid A correlated with restriction fragment length polymorphisms in the Saa gene determined by Taylor and Rowe (1984). Analysis of a number of highly diverged species of mice indicated that AGP expression has undergone considerable modification during evolution of the Mus genus; this is associated with alterations in Agp gene organization, which may include species-specific amplification and/or deletion events.
    Type of Medium: Electronic Resource
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