title: The measurement accuracy required for acceptable estimation of steady and non-steady rates of appearance and disappearance from the inaccessible compartment of an open, two-compartment system.
abstract: A two-compartment system for measuring non-steady state turnover rates was examined by computer simulation. Tracee appears de novo in a compartment to which the experimenter has no access, and from which material is irreversibly lost. In the steady state, Monte Carlo analysis showed that the compartment sizes and fluxes could be determined by tracer experiments with reasonable accuracy. In contrast, under non-steady state conditions, the results proved extremely sensitive to observational uncertainties. Given perfectly accurate input data, simulation showed that the calculated turnover rates agreed closely with the true answer, although not perfectly because of the necessity for interpolation. Contaminating the input data with a single erroneous observation of either tracee or tracer concentration produced large, spurious oscillations in the calculated turnover rates, the duration of which was inversely proportional to the frequency with which the infused compartment was sampled. Contaminating the input data with observational noise of a magnitude likely in practice so degraded the results that they became almost unusable. It is concluded that non-steady state measurements are feasible using this model, but that rapid sampling and random uncertainties smaller than 1% (coefficient of variation) are desirable in the measurement of tracer and tracee concentration.
mesh_terms: D003201:Computers; D007700:Kinetics; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations