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  • Title: Application of a simple competitive protein-binding assay technique to the pharmacokinetics of N-(phosphonacetyl)-L-aspartate in humans.
    Author: Erlichman C, Strong JM, Chabner BA.
    Journal: Cancer Res; 1980 Jun; 40(6):1902-6. PubMed ID: 7371023.
    Abstract:
    A competitive protein-binding assay for N-(phosphonacetyl)-L-aspartate (PALA) using aspartate transcarbamylase as the receptor protein and [14C]PALA as the radioactive ligand is described here and has been applied to study the pharmacokinetics of PALA in humans. A protein-free ultrafiltrate of plasma, prepared by centrifugation of 1-ml samples through Amicon Centriflo membrane cones, was used in the assay, which had a maximun sensitivity of 0.7 microM PALA in plasma. At this level, the coefficient of variation was less than 10%. Comparison of the competitive binding assay to a gas chromatographic-mass spectrometric technique shows that the two methods yield equivalent results in the concentration range of 1 microM to 1 mM. However, the competitive binding assay possesses practical advantages because of its simplicity and the ease with which multiple samples may be assayed. PALA disappearance from plasma was studied in seven patients and was found to be consistent with a two-compartment open model. The t1/2 alpha (elimination half-life for initial phase) and t1/2 beta (elimination half-life for terminal phase) were 0.93 +/- 0.73 (S.D.) hr and 4.82 +/- 1.48 hr, respectively. The cumulative urinary excretion of PALA int two patients was 70 and 90% of the administered dose 16 hr after the infusion was completed.
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