The early plasma concentration of : a comparison of three models51: a comparison of three modelsCr-EDTA in patients with cirrhosis and ascites: a comparison of three models

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Abstract

Objectives

The aim of the study was to determine which of three two-parameter fitting functions (exponential, linear-log, and negative-power function of time) most accurately models early chromium-51-EDTA (51Cr-EDTA) plasma concentration data prior to 120 min in patients with cirrhosis and ascites and understand how these fitting functions affect the calculation of the area under the plasma concentration curve (AUC).

Methods

A bolus, antecubital intravenous injection of 2.6 MBq of 51Cr-EDTA was given to 13 patients with cirrhosis and ascites. Up to 16 blood samples were drawn at time points ranging from 5 to 1440 min following injection. The concentration data prior to 120 min were used as reference data. Early time concentration values, estimated by fitting exponential, linear-log, and negative-power functions of time to the time samples at 120, 180, and 240 min, were then compared with reference data. The AUC was calculated for each patient using the exponential, Bröchner-Mortensen-corrected exponential, and linear-log functions, and these values were compared.

Results

The withheld, observed plasma concentrations were (a) most accurately estimated by linear-log functions (Wilcoxon P=0.4548), (b) significantly underestimated by exponential functions (Wilcoxon P=0.0002), and (c) significantly overestimated by negative-power functions (Wilcoxon P=0.0034). The relative errors when ranked from best to worst were those for the linear-log (12.0%, 9.0%), exponential (22.9%, 14.2%), and negative-power (31.9%, 48.4%) functions of time, respectively (median, interquartile range). For each patient, the values for AUC calculated by the exponential function differed significantly (range=3.4–15.3%, median=8.3%) from those calculated by the corrected Bröchner-Mortensen exponential, as to a lesser extent did those values calculated using linear-log functions (range=0.4–8.0%, median=3.0%).

Conclusion

In patients with cirrhosis, linear-log functions were significantly more accurate than exponential or power functions in estimating early time plasma concentrations (<120 min). However, the improved linear-log early time plasma concentration model does not provide as much correction to the total AUC as does the corrected Bröchner-Mortensen exponential method. This is likely because of the large contribution of late time data to the AUC, and future work is suggested to explore the late time fit problem.

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