Endothelial uptake of drugs hormones and metabolites

J. H. Linehan*, C. A. Dawson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Three different first-pass organ extraction approaches have been used to quantify nonlincar pulmonary endothelial and/or metabolism process. In each, the saturable process is modeled using the Michaelis-Menten equation. Direct comparison of kinetic parameter estimates from (1) serial constant substrate infusions (2) multiple indicator dilution injections of tracer substrates during the constant infusions and (3) serial multiple indicator dilution injections containing successively larger amounts of substrate delineate the impact of specific assumptions underlying the mathematical models used in each approach. The substrate used was benzoly-Phe-Ala-Pro (BPAP). The transform of BPAP is hydrolyzed by angiotensin-converting enzyme located on the luminal surface of the pulmonary endothelium. Estimates of Vmax (maximum rate of hydrolysis) and Km (concentration at half Vmax) obtained from the three methods were not statistically different. Thus, for surface enzyme substrates the differences between approaches are not quantitatively important relative to factors contributing random errors to each approach. The choice of approach can, therefore, be made on practical grounds.

Original languageEnglish (US)
Number of pages1
JournalAnnals of Biomedical Engineering
Volume19
Issue number5
StatePublished - Dec 1 1991

ASJC Scopus subject areas

  • Biomedical Engineering

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