臺灣博碩士論文加值系統

生理學原理的人體藥物動力學模式(Physiologically Based Pharmacokinetic model，簡稱PBPK模式)在近年已漸被採用於職場風險評估或其相關課題研究，以作為法定環境暴露指標的依據。本文利用PBPK模式以描述人體暴露於有害化學物質，經過適當的生理與代謝機制後，該化學物質或其代謝物的殘存於體內隨時間變化的濃度。然而PBPK模式的計算，由於牽涉許多未知且無法直接量取的人體參數，而且這些參數會因人而異。因此，其參數的估計與模式的建立，從統計學的觀點而言，缺乏說服力與合法性。本文說明如何將一個簡化的PBPK模式轉換成隨時間變化的混合線性模式，用以進行統計推估。另外本文還探討在適當的實設計下所需的量測次數與樣本數。最後針對混合線性模式以二種化學物質的一些實驗參數代入模擬人體體內濃度，從模擬實驗評估模式的可信度。之後再以一筆從塑膠工廠實際量測工人暴露於氯乙烯之下 ，工人尿液中檢測得到的TdGA代謝物濃度，套用於本文的模式為例，說明此方法的可行性。

Physiologically-based pharmaco-kinetic (PBPK) model has been used in occupational risk assessment and related research topics in recent years. A typical PBPK model can be applied to describe the time dependent internal concentrations or its metabolites after being exposed to environmental toxic chemicals. However, owing to large numbers of unknown parameters which are dependent on individualism, the solutions by a PBPK model may lack legitimacy from a statistical point of view. This research explains how one can transform a single compartment pharmaco-kinetic model into a time —dependent mixed linear model, in order to make statistical inference with out difficulty. Experiment designs for the number of visits and required sample size to achieve desired statistical power are explored. Two chemicals, methyl chloroform and vinyl chloride, for this internal concentrations relative to this TLV’s are simulated. Also, the proposed mixed linear model is applied to is VCM workers data as an example. The results indicated that the method is appropriate.

目錄
Ch1.前言……………………………………………… 1
Ch2.統計方法…………………………………………14
2.1從藥物動力學模式推導而得的統計混合模式
…………………………………………………14
2.2 未知參數之估計………………………………20
Ch3.實驗設計…………………………………………24
3.1重覆量測次數的相對量測效率(relative
efficiency) …………………………………24
3.2在固定的效度之下樣本數的估計……………30
Ch4.模擬實驗與實例應用……………………………35
4.1模擬實驗………………………………………35
4.2實例應用………………………………………46
Ch5.結論………………………………………………56
參考文獻………………………………………………59

參考文獻
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