AJP - Regulatory, Integrative and Comparative Physiology, Vol 257, Issue 1 237-R245, Copyright © 1989 by American Physiological Society
Allopurinol kinetics in humans as a means to assess liver function: design of a loading test
G. Van Waeg and T. Groth
Department of Clinical Chemistry, Uppsala University, Sweden.
A six-compartment model of allopurinol and oxipurinol kinetics, after
intravenous allopurinol injection in the human, is studied further to
improve the blood and urine specimen collection schedule for clinical use.
The effects of various error sources are also investigated by simple
techniques like real data set truncation and adding normally distributed
random errors to data obtained from simulation of allopurinol and
oxipurinol plasma curves with preset parameters. All parameters estimation
is performed with the NONLIN parameter estimation program. Main interest
was focused on estimation of the fractional rate constant of transport from
the central "extracellular" compartment to the metabolically active
compartment. This parameter is regarded as a lumped measure of liver
perfusion and liver cell membrane transport. The blood sampling schedule
can be reduced to six specimens collected over 60 min, without affecting
the accuracy and precision of estimated clinical parameters. The maximum
allowable coefficient of variation for preanalytical errors and the
analytical within-run and between-run errors are around 5, 4, and 5%,
respectively. Analytical between-run bias up to 20% does not affect the
estimate of the principal parameter, when both allopurinol and oxipurinol
are biased in the same direction. Collection and analysis of urine samples
was shown to be unnecessary.
