Application of a simple competitive protein-binding assay technique to the pharmacokinetics of N-(phosphonacetyl)-L-aspartate in humans

C. Erlichman, J. M. Strong, B. A. Chabner

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 phamacokinetics 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 maximum sensitivity of 0.7 μM 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 μM to 1mM. 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 t(1/2α) (elimination half-life for initial phase) and t(1/2β) (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 in two patients was 70 and 90% of the administered dose 16 hr after the infusion was completed.

Original languageEnglish (US)
Pages (from-to)1902-1906
Number of pages5
JournalCancer Research
Volume40
Issue number6
StatePublished - 1980
Externally publishedYes

Fingerprint

NSC 224131
Competitive Binding
Protein Binding
Aspartic Acid
Pharmacokinetics
Half-Life
Aspartate Carbamoyltransferase
Centrifugation
Proteins
Gases
Ligands
Membranes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Application of a simple competitive protein-binding assay technique to the pharmacokinetics of N-(phosphonacetyl)-L-aspartate in humans. / Erlichman, C.; Strong, J. M.; Chabner, B. A.

In: Cancer Research, Vol. 40, No. 6, 1980, p. 1902-1906.

Research output: Contribution to journalArticle

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