Criteria for reporting noncompartmental estimates of half-life and area under the curve extrapolated to infinity

Abstract

Various criteria have been proposed for determining the reliability of noncompartmental pharmacokinetic estimates of the terminal disposition phase half-life (t_1/2 ) and the extrapolated area under the curve (AUC_extrap ). This simulation study assessed the performance of two frequently used reportability rules: the terminal disposition phase regression adjusted-r² classification rule and the regression data point time span classification rule. Using simulated data, these rules were assessed in relation to the magnitude of the variability in the terminal disposition phase slope, the length of the terminal disposition phase captured in the concentration-time profile (data span), the number of data points present in the terminal disposition phase, and the type and level of variability in concentration measurement. The accuracy of estimating t_1/2 was satisfactory for data spans of 1.5 and longer, given low measurement variability; and for spans of 2.5 and longer, given high measurement variability. Satisfactory accuracy in estimating AUC_extrap was only achieved with low measurement variability and spans of 2.5 and longer. Neither of the classification rules improved the identification of accurate t_1/2 and AUC_extrap estimates. Based on the findings of this study, a strategy is proposed for determining the reportability of estimates of t_1/2 and area under the curve extrapolated to infinity.

Keywords: area under the curve (AUC); half-life; noncompartmental data analysis (NCA); pharmacokinetics.