Histogram analysis of pharmacokinetic parameters by bootstrap resampling from one-point sampling data in animal experiments.
A bootstrap method is proposed for assessing statistical histograms of pharmacokinetic parameters (AUC, MRT, CL and V(ss)) from one-point sampling data in animal experiments. A computer program, MOMENT(BS), written in Visual Basic on Microsoft Excel, was developed for the bootstrap calculation and the construction of histograms. MOMENT(BS) was applied to one-point sampling data of the blood concentration of three physiologically active proteins ((111)In labeled Hsp70, Suc(20)-BSA and Suc(40)-BSA) administered in different doses to mice. The histograms of AUC, MRT, CL and V(ss) were close to a normal (Gaussian) distribution with the bootstrap resampling number (200), or more, considering the skewness and kurtosis of the histograms. A good agreement of means and SD was obtained between the bootstrap and Bailer's approaches. The hypothesis test based on the normal distribution clearly demonstrated that the disposition of (111)In-Hsp70 and Suc(20)-BSA was almost independent of dose, whereas that of (111)In-Suc(40)-BSA was definitely dose-dependent. In conclusion, the bootstrap method was found to be an efficient method for assessing the histogram of pharmacokinetic parameters of blood or tissue disposition data by one-point sampling.
Takemoto
Seiji
S
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Science, Kyoto University.
Yamaoka
Kiyoshi
K
Nishikawa
Makiya
M
Takakura
Yoshinobu
Y
D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D015233:Models, Statistical; D009010:Monte Carlo Method; D010599:Pharmacokinetics; D012709:Serum Albumin / Q000008:administration & dosage / Q000493:pharmacokinetics; D012984:Software
D018840:HSP70 Heat-Shock Proteins; D012709:Serum Albumin; C034877:succinylalbumin