Simulation for Clinical Repeated-Dose Pharmacokinetic Trials Applying a Peak-and-Trough Sampling Design to Estimate Oral Clearance(Biopharmacy)
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概要
- 論文の詳細を見る
We performed a simulation for the clinical pharmacokinetic study, in which blood was sampled at two time points corresponding to the peak concentration (C_<peak>) and trough concentration (C_<trough>) following repetitive oral drug administration to subjects. We estimated the approximate oral clearance (CL/F_<approx>) as 2・D/(C_<peak>・τ+C_<trough>・τ), where D is the dose, and τ is the dosing interval. The CL/F_<approx> value was accurate for drugs with a long-elimination half-life, and the estimation error of the CL/F value was slightly increased for drugs with a shorter elimination half-life. The accuracy of CL/F_<approx> in each subject was not affected by the magnitude of the interindividual pharmacokinetic variability, but was significantly decreased by the larger measurement error of drug concentrations (or intraindividual pharmacokinetic variability). We further performed several computer simulations to mimic statistical hypothesis testing following the clinical repeated-dose pharmacokinetic trials. The statistical power to detect the difference of oral clearance between two groups was marginally dependent on the measurement error of drug concentration, but was highly dependent on the interindividual pharmacokinetic variability. These findings suggested that the peak-and-trough sampling design to CL/F_<approx> value is useful for clinical repeated-dose pharmacokinetic trials, and that the study design and protocol should be evaluated carefully by computer simulation prior to a real clinical trial.
- 公益社団法人日本薬学会の論文
- 2007-11-01
著者
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TAGUCHI Masato
Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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HASHIMOTO Yukiya
Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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Hashimoto Y
Graduate School Of Pharmaceutical Sciences Kyushu University
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Kayano Yuichiro
Graduate School Of Medicine And Pharmaceutical Sciences University Of Toyama
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Hashimoto Yuichi
Institute Of Molecular & Cellular Biosciences University Of Tokyo
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Harada Yuichi
Center For Influenza Virus Research National Institute Of Infectious Diseases
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Ishida Kazuya
Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama
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Taguchi Masato
Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama
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Hashimoto Yukiya
Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama
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Hashimoto Y
Institute Of Molecular & Cellular Biosciences The University Of Tokyo
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Hashimoto Yuichi
Institute of Molecular & Cellular Biosciences, The University of Tokyo
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