鼻腔噴霧器體外生體相等性統計評估：小霧滴大小分佈

Statistical Evaluation of In Vitro Bioequivalence for Nasal Aerosols and Nasal Sprays for Local Action：Droplet size Distribution

游忠憲(Chung-hsien Yue)

指導教授 ： 劉仁沛

國立臺灣大學/生物資源暨農學院/農藝學研究所/碩士(2008年)

https://doi.org/10.6342/NTU.2008.10633

摘要

為了學名與原廠鼻腔噴霧器之生體相等性，本論文藉由與標準鼻腔噴霧器的噴霧效果來做比較是否為生體相等。在試驗過程中，因噴霧藥效為局部性的，並不會進入血液而影響其他身體器官，未避免人體實驗中包含的變異(如：力道、吸氣量…等)，所以以機器實驗來取代人體實驗。在分析過程中，我們關注的有噴霧樣本、小霧滴大小分佈及雲霧狀幾何學，而分析方法是採用非剖析分析(nonprofile analyses)。最後的判定準則是將我們的標準線性化後，去觀測其95%信賴區間的上界，依結果判定學名噴霧器是否與原廠噴霧器為生體相等性。

關鍵字

鼻腔噴霧器,小霧滴大小分佈,噴霧樣本,雲霧狀幾何學,線性標準

並列摘要

In order to evaluate bioequivalence between the generic and innovator investigate the equivalence in characteristics between the generic and innovator nasal aerosols. Because the nasal aerosols only act locally and its active ingredient does not absorb into the body system, therefore in vivo bioequivalence studies are replaced by the in vitro bioequivalence studies using machinery experiment to avoid variability caused the factors much that volume of breath. The quality of nasal aerosols and sprays can be characterized by spray patterns, droplet size distribution and plume geometry. The 2003 US FDA draft guidance proposed the application of population bioequivalence to evaluate the in vitro bioequivalence between the generic and innovator nasal aerosols and sprays. Such analysis is referred to as the nonprofile analysis. We applied the statistical methods of in vitro bioequivalence in the US FDA guidance to a dataset of droplet size distribution. We also compare and discuss the results obtained under the 2-stage nested random-effects model and the model suggested in the 2003 US FDA draft guidance.

並列關鍵字

Nasal Aerosols, Droplet Size Distribution, Spray Pattern, Plume Geometry, Linearized Criterian

參考文獻

Hyslop T., F. Hsuan, D.J. Holder, “A small-sample confidence interval approach to assess individual bioequivalence,” Statistics in Medicine, 19, 2885-2899, 2000.

Howe W.G., “Approximate confidence limits on the mean of X+Y where X and Y are two tabled independent random variables”. J Amer Statist Assoc, 69:789-794, 1974.

Ting N., R.K. Burdick, F.A. Graybill, S. Jeyaratnam, T.-F.C.Lu, “Confidence intervals on linear combinations of variance components that are unrestricted in sign”. J Statist Computation and Simulation, 35, 135-143, 1990.

FDA Guidance for Industry on Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for local Action, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, April 2003.

Hsu J.C., J.T.G.Hwang, H.-K. Liu, and S.J. Ruberg, “Confidence intervals associated with tests for bioequivalence”. Biometrika, 81:103-114, 1994.