Prediction accuracy of pharmacokinetic parameters is often assessed using prediction fold error, i.e., being within 2-, 3-, or n-fold of observed values. However, published studies disagree on which fold error represents an accurate prediction. In addition, "observed data" from only one clinical study are often used as the gold standard for in vitro to in vivo extrapolation (IVIVE) studies, despite data being subject to significant interstudy variability and subjective selection from various available reports. The current study involved analysis of published systemic clearance (CL) and volume of distribution at steady state (V_ss) values taken from over 200 clinical studies. These parameters were obtained for 17 different drugs after intravenous administration. Data were analyzed with emphasis on the appropriateness to use a parameter value from one particular clinical study to judge the performance of IVIVE and the ability of CL and V_ss values obtained from one clinical study to "predict" the same values obtained in a different clinical study using the n-fold criteria for prediction accuracy. The twofold criteria method was of interest because it is widely used in IVIVE predictions. The analysis shows that in some cases the twofold criteria method is an unreasonable expectation when the observed data are obtained from studies with small sample size. A more reasonable approach would allow prediction criteria to include clinical study information such as sample size and the variance of the parameter of interest. A method is proposed that allows the "success" criteria to be linked to the measure of variation in the observed value.

Purpose. Gastric emptying (GE) is often reported to be slower and more irregular in premature neonates than in older children and adults. The aim of this study was to investigate the impact of age and other covariates on the rate of GE. Methods. The effect of age on the mean gastric residence times (MGRT) of liquid and solid food was assessed by analysing 49 published studies of 1457 individuals, aged from 28 weeks gestation to adults. The data were modelled using the nonlinear mixed‐effects approach within NONMEM version 7.2 (ICON, Dublin, Ireland), with evaluation of postnatal age, gestational age and meal type as covariates. A double Weibull function was selected as a suitable model since it could account for the typical biphasic nature of GE. Results. Age was not a significant covariate for GE but meal type was. Aqueous solutions were associated with the fastest emptying time (mean simulated gastric residence time of 45 min) and solid food was associated with the slowest (98 min). Conclusions. These findings challenge the assertion that GE is different in neonates, as compared with older children and adults due to age, and they reinforce the significance of food type in modulating GE. © 2015 The Authors. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd.