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 Vss) 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...

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Bibliographic Details
Published in:DRUG METABOLISM AND PHARMACOKINETICS 2006-01, Vol.21 (6), p.458-464
Main Authors: Takemoto, Seiji, Yamaoka, Kiyoshi, Nishikawa, Makiya, Takakura, Yoshinobu
Format: Article
Language:English
Subjects:
Algorithms
Animals
Area Under Curve
bootstrap method
histogram analysis
HSP70 Heat-Shock Proteins - administration & dosage
HSP70 Heat-Shock Proteins - pharmacokinetics
hypothesis testing
Mice
Models, Statistical
Monte Carlo
Monte Carlo Method
Pharmacokinetics
Serum Albumin - administration & dosage
Serum Albumin - pharmacokinetics
Software
sparse sampling
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Summary:A bootstrap method is proposed for assessing statistical histograms of pharmacokinetic parameters (AUC, MRT, CL and Vss) 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 (111In labeled Hsp70, Suc20-BSA and Suc40-BSA) administered in different doses to mice. The histograms of AUC, MRT, CL and Vss 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 111In-Hsp70 and Suc20-BSA was almost independent of dose, whereas that of 111In-Suc40-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.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.21.458