(3.236.222.124) 您好!臺灣時間:2021/05/10 15:58
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

: 
twitterline
研究生:曾傳志
研究生(外文):TSENG, CHUAN-CHIH
論文名稱:以腎絲球過濾率(GFR)成熟模型預測小兒之藥物清除率
論文名稱(外文):Prediction of Pediatric Drug Clearance Using Growth and Maturation Models for GFR
指導教授:胡德民胡德民引用關係
指導教授(外文):HU, TEH-MIN
口試委員:胡明寬張豫立康孝先胡德民
口試委員(外文):HU, MING-KUANCHANG, YU-LIKANG, HSIAO-HSIENHU, TEH-MIN
口試日期:2017-05-12
學位類別:碩士
校院名稱:國防醫學院
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:204
中文關鍵詞:藥物清除率腎絲球過濾率
外文關鍵詞:Drug clearanceGlomerular filtration rateAllometryGrowth and maturation models
相關次數:
  • 被引用被引用:0
  • 點閱點閱:125
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:8
  • 收藏至我的研究室書目清單書目收藏:0
研究背景:在藥品的開發過程中,較少納入幼兒以獲取藥動學參數相關資料,因此長久以來,在幼兒的給藥劑量上,經常是以經驗法則依照體重或年紀來推估。然而我們必須知道的是,幼兒並非僅只是個體較小的成年人,意即幼兒與成人間發展程度(development)的不同,並非僅用簡單的線性關係就可以解釋。近年以來已有許多學者提出了較複雜的模型,綜合考量成長(growth)與成熟(maturation)因子,來闡述由幼兒至成人其清除率的發展過程,而且也獲得了不錯的成果。然而,由於各個藥品間的物化性質原本就存在差異,在體內被代謝的程度與排除的模式也各自不同,因此這些模型的參數常需要隨著探討藥品的不同而改變,似乎僅用固定的參數無法通用於所有藥品。
研究目的:(1) 希望建立一個能預測從出生到成年藥品清除率的通用模式,適用於主要經由腎臟排除的藥品,基本的假設是建立在人體對藥品清除能力的成熟過程,應與腎絲球過濾速率(GFR)的成熟過程具高度相關性。(2) 進行各種預測模式的比較,嘗試找到較佳的描述模式。(3) 針對各種腎功能指標如GFR,腎血流速率與腎小管主動分泌速率,探討腎功能的成熟過程與藥品清除能力的成熟過程,兩者間的相關性。
研究方法:我們納入了四個GFR成熟模型與兩個型態大小模型(allometric scaling model)來預測不同年齡的幼兒藥品清除率,清除率數據取自過去文獻所記載的資料。此外我們亦以模擬的方式來創造虛擬真實清除率(基於WHO/CDC提供的幼兒生長資料)。模型的預測準確性則以RMSE、AAFE、AFE和FE來做評估。另外我們也以Hayton等2位學者所提的GFR預測公式來探討GFR與藥品清除能力發展(或成熟)過程的相關性。
研究結果:總共納入了868個清除率數據與1628個虛擬真實清除率來作分析。其中,此文獻收集之清除率數據總共包含了39種不同性質的藥品。GFR成熟模型在預測年紀較小的幼兒上,其預測準確性似乎是優於型態大小模型,但是在年紀超過2歲以上的幼兒,這些模型的預測準確性是無明顯差別的,意即可能在年紀超過2歲以上的幼兒,單純用型態大小模型即可達到不錯的清除率預測結果。其中,在整體的預測準確性上,似乎以Hayton的GFR成熟模型表現較好,而且以此預測模型使用上的便利性較佳,因其不需隨著藥品的不同而改變公式內的參數值,即可達到不錯的預測結果。另外我們亦發現,在三種腎功能指標中(腎絲球過濾速率、腎小管主動分泌速率、腎血流速率),以腎絲球的過濾速率較能適切的描述大部分藥品清除能力的發展過程(development)。另外本研究亦顯示腎絲球過濾速率的成熟過程與藥品清除能力的成熟過程兩者之間具良好的關聯性。
結論:由本研究中可看出,GFR成熟模型應可以固定參數而通用於主要經由腎臟排除的藥品其清除率預測。另外,GFR的成熟過程應可用於描述藥品清除能力的成熟過程。
Background: Pediatric dosing information is not routinely acquired during the drug development process, and empirical rules based on body weight or age are often used for estimating doses in pediatric patients. However, “children are not small adults”the difference between children and adults cannot be realized by a simple linear function of body weight or age. Recently, more complex mathematical models have been proposed to describe the changes of drug clearance at different ages from birth to adulthood. These models account for growth and maturation in child development, and have been applied successfully to a wide variety of drugs. Since drugs have diverse pharmacokinetic properties, with varied dependence on hepatic metabolism and renal excretion, the maturation model often includes drug-specific parameter values for a particular drug; and generalizability is difficult, or not impossible.
Objectives: The objectives of the present study are (1) to investigate whether a general model can be used for predicting the clearance values of mainly renally excreted drugs based on the assumption that GFR maturation may account for the maturation of renal drug-eliminating ability; (2) to compare the prediction performance among various prediction models; and (3) to investigate the relationship between the maturation of renal function indices (e.g. GFR, renal blood flow rate, and active tubular secretion rate) and the maturation of drug elimination in the human body.
Methods: Four GFR maturation models and two allometric scaling models (size models) were included to predict drug clearance (CL) at different child ages. Real, observed CL values were obtained from published studies through a PubMed-based text-mining procedure. Besides, simulations were conducted to generate simulated CL values (based on the WHO/CDC growth chart). Predictive performance was evaluated using various precision and accuracy measures (e.g. RMSE, AFE, and AAFE). Besides, two specific models (Hayton GFR vs. Mahmood GFR) were used to describe the relationship between maturation of renal function and that of drug elimination.
Results: A total of 868 exact and 1628 simulated CL values were included for analysis. The exact CL values are from 39 drugs, spanning various therapeutic categories. The maturation models generally have better predictive performance than the size models in younger ages; however, at 2 years of age and above, the prediction accuracy seems to be similar, suggesting that the size model alone can be used for the prediction of drug clearance at ages above 2 years. Remarkably, among all the maturation models, the Hayton equation provides the best predictions. The advantage and attractiveness of using a GFR maturation model based on the Hayton equation is that a general equation with a limited number of parameters can be used in predicting drug CL values for a wide variety of drugs at different human developmental stages. Besides, we found that among the three indicators of renal function (GFR, tubular active secretion, renal blood flow), GFR maybe the best parameter to describe the development of drug-eliminating ability.
Conclusions: The study demonstrates that the GFR maturation models may be used as a general model for predicting the total clearance of drugs that are mainly excreted from the kidneys. The study further shows that the development of human drug elimination capability is closely related to the maturation process of GFR.
正文目錄
第一章、 緒論 1
第一節、 研究背景與動機 1
壹、 小兒與成人在藥物動力學上的差異 1
一、 吸收 1
二、 分佈 3
三、 代謝 4
四、 排除 9
貳、 劑量和清除率之間的關係 12
第二節、 小兒清除率(劑量)預測方法的歷史性回顧 13
壹、 經驗法則 13
貳、 型態大小模型(Size model) 16
一、 型態大小模型-指數3/4 (fixed exponent-3/4 AS model) 18
二、 型態大小模型-指數隨年紀調整(Age-dependent exponent) 20
三、 型態大小模型-指數隨體重調整(Body weight-dependent exponent) 21
參、 成熟度模型(Maturation model) 22
肆、 群體藥動學統計分析模型 (Population pharmacokinetic- statistic model) 25
伍、 以生理學為基礎之藥動學模型(Physiologically based pharmacokinetic model,PBPK model) 27
陸、 其他模型 28
第三節、 研究目的 32
第二章、 研究方法 34
第一節、 文獻搜尋 37
壹、 建立藥物清單 37
貳、 收集文獻所載真實清除率數據 38
參、 文獻數據分析與篩選 38
第二節、 創造虛擬真實清除率 39
壹、 創造虛擬個體 39
貳、 建立虛擬真實清除率 39
第三節、 預測模型的建立 42
第四節、 納入文獻所提其他預測模型 45
壹、 型態大小模型-指數3/4 (fixed exponent-3/4 AS model) 45
貳、 型態大小模型-指數隨年紀調整(Age-dependent exponent) 45
第五節、 比較不同模型預測準確度 46
壹、 Root Mean Square Error(RMSE) 46
貳、 Average Fold Error(AFE) 47
參、 Absolute Average Fold Error(AAFE) 47
肆、 Fold Error(FE) 47
第六節、 探討腎功能與藥品清除率成熟過程 48
第三章、 研究結果 52
第一節、 文獻數據分析與篩選結果 52
第二節、 虛擬真實清除率建立結果 54
第三節、 真實清除率預測結果 55
第四節、 虛擬真實(simulated true)清除率預測結果 69
第五節、 藥物清除率發展與成熟程度分佈結果 71
第四章、 研究討論 80
第五章、 結論 102


表目錄
表 1、計算小兒劑量的經驗法則 14
表 2、其他文獻所提清除率預測模型 29
表 3、六種預測模型的RMSE、AFE、AAFE和FF (預測文獻中收集得來之清除率) 67
表 4、在不同年齡分層時,幼兒個體間清除率成熟度(相對於成人)變異性狀況 68
表 5、六種預測模型的RMSE、AFE、AAFE和FF (預測虛擬清除率) 70


圖目錄
圖 1、主要的CYP450s代謝酵素亞型(A)和CYP3A7(B)的個體發生學 7
圖 2、CYPs代謝酵素成熟曲線圖 8
圖 3、研究方法流程圖 35
圖 4、文獻搜尋流程圖 36
圖 5、六種預測模型的RMSE、AFE、AAFE和FF的比較 57
圖 6、六種預測模型落在不同Fold Error區間個數百分比的比較 58
圖 7、GFR Model (eGFR, Hayton)在各齡層的Fold Error分布狀況 61
圖 8、Allometric Model (Exponent 0.75)在各齡層的Fold Error分布狀況 62
圖 9、Allometric Model (Exponent: ADE)在各齡層的Fold Error分布狀況 63
圖 10、GFR Model (eGFR, ADE, Mahmood)在各齡層的Fold Error分布狀況 64
圖 11、GFR Model (eGFR, Mat, Mahmood)在各齡層的Fold Error分布狀況 65
圖 12、GFR Model (eGFR, Mat, Rhodin)在各齡層的Fold Error分布狀況 66
圖 13、腎功能指標及清除率發展程度分佈曲線 72
圖 14、標準化GFR(GFR依Hayton equation)與標準化清除率成熟程度分佈曲線 74
圖 15、標準化GFR(GFR依Mahmood equation)與標準化清除率成熟程度分佈曲線 75
圖 16、標準化GFR(GFR依Hayton equation)與幾何平均標準化清除率成熟程度分佈曲線 77
圖 17、標準化GFR(GFR依Mahmood equation)與幾何平均標準化清除率成熟程度分佈曲線 78
圖 18、GFR成熟程度與清除率成熟程度相關性分佈狀況 79
圖 19、3種GFR預測公式描述GFR隨著體重變化之關係圖 85
圖 20、3種GFR預測公式描述GFR成長速度(dGFRdBW)隨著體重變化之關係圖 86
圖 21、GFR model(eGFR,Hayton)針對年紀低於28天的幼兒清除率預測準確性。(右圖均各自為描述左圖FE值超過5以上的部分) 92
圖 22、Amikacin清除率落點分佈圖 96
圖 23、Amikacin清除率落點分佈圖(放大文獻3清除率落點) 97
圖 24、Baclofen清除率落點分佈圖 98



附表目錄
附錄1、清除率來源文獻之內容摘要……………………………….............121
附錄2、清除率來源藥品之性質摘要……………………………………….188
附錄3、文獻中藥品清除率數值收集遭遇問題及解決方式……………..202
附錄4、清除率分組方式說明(依據腎臟血流與腎絲球過濾速率)…...203
1.Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. The New England journal of medicine. 2003 Sep 18;349:1157-67.
2.Anderson GD, Lynn AM. Optimizing pediatric dosing: a developmental pharmacologic approach. Pharmacotherapy. 2009 Jun;29:680-90.
3.Agunod M, Yamaguchi N, Lopez R, Luhby AL, Glass GB. Correlative study of hydrochloric acid, pepsin, and intrinsic factor secretion in newborns and infants. The American journal of digestive diseases. 1969 Jun;14:400-14.
4.Hyman PE, Clarke DD, Everett SL, Sonne B, Stewart D, Harada T, et al. Gastric acid secretory function in preterm infants. The Journal of pediatrics. 1985 Mar;106:467-71.
5.Bartelink IH, Rademaker CM, Schobben AF, van den Anker JN. Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clinical pharmacokinetics. 2006;45:1077-97.
6.Huang NN, High RH. Comparison of serum levels following the administration of oral and parenteral preparations of penicillin to infants and children of various age groups. The Journal of pediatrics. 1953 Jun;42:657-8.
7.McLeod HL, Relling MV, Crom WR, Silverstein K, Groom S, Rodman JH, et al. Disposition of antineoplastic agents in the very young child. The British journal of cancer Supplement. 1992 Aug;18:S23-9.
8.Strolin Benedetti M, Baltes EL. Drug metabolism and disposition in children. Fundamental & clinical pharmacology. 2003 Jun;17:281-99.
9.Bouzom F, Walther B. Pharmacokinetic predictions in children by using the physiologically based pharmacokinetic modelling. Fundamental & clinical pharmacology. 2008 Dec;22:579-87.
10.Linday L, Dobkin JF, Wang TC, Butler VP, Jr., Saha JR, Lindenbaum J. Digoxin inactivation by the gut flora in infancy and childhood. Pediatrics. 1987 Apr;79:544-8.
11.Ayrton A, Morgan P. Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica; the fate of foreign compounds in biological systems. 2001 Aug-Sep;31:469-97.
12.Lu H. Prediction of Heptatic and Renal Clearance in pediatric Populations: A "Bottom-Up" Approach Versus "Top-Down" Recognition of Covariates. 2013.
13.Kearns GL. Impact of developmental pharmacology on pediatric study design: overcoming the challenges. The Journal of allergy and clinical immunology. 2000 Sep;106:S128-38.
14.Furue M, Terao H, Rikihisa W, Urabe K, Kinukawa N, Nose Y, et al. Clinical dose and adverse effects of topical steroids in daily management of atopic dermatitis. The British journal of dermatology. 2003 Jan;148:128-33.
15.Friis-Hansen B. Body water compartments in children: changes during growth and related changes in body composition. Pediatrics. 1961 Aug;28:169-81.
16.McNamara PJ, Alcorn J. Protein binding predictions in infants. AAPS pharmSci. 2002;4:E4.
17.Cresteil T. Onset of xenobiotic metabolism in children: toxicological implications. Food additives and contaminants. 1998;15 Suppl:45-51.
18.Lu H, Rosenbaum S. Developmental pharmacokinetics in pediatric populations. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG. 2014 Oct-Dec;19:262-76.
19.Levy G, Khanna NN, Soda DM, Tsuzuki O, Stern L. Pharmacokinetics of acetaminophen in the human neonate: formation of acetaminophen glucuronide and sulfate in relation to plasma bilirubin concentration and D-glucaric acid excretion. Pediatrics. 1975 Jun;55:818-25.
20.Anderson BJ, Holford NH. Mechanism-based concepts of size and maturity in pharmacokinetics. Annual review of pharmacology and toxicology. 2008;48:303-32.
21.van den Anker JN, Schwab M, Kearns GL. Developmental pharmacokinetics. Handbook of experimental pharmacology. 2011;205:51-75.
22.Solhaug MJ, Bolger PM, Jose PA. The developing kidney and environmental toxins. Pediatrics. 2004 Apr;113:1084-91.
23.Morselli PL, Franco-Morselli R, Bossi L. Clinical pharmacokinetics in newborns and infants. Age-related differences and therapeutic implications. Clinical pharmacokinetics. 1980 Nov-Dec;5:485-527.
24.Loebstein R, Koren G. Clinical pharmacology and therapeutic drug monitoring in neonates and children. Pediatrics in review. 1998 Dec;19:423-8.
25.Shargel L, Yu A. Drug clearance. In: Introduction to pharmacokinetics. Applied Biopharmaceutics and pharmacokinetics 3rd ed Norwalk, Appleton & Lange. 1993:265-92.
26.Rubin MI, Bruck E, Rapoport M, Snively M, McKay H, Baumler A. MATURATION OF RENAL FUNCTION IN CHILDHOOD: CLEARANCE STUDIES. The Journal of clinical investigation. 1949 Sep;28:1144-62.
27.Jones DP, Chesney RW. Development of tubular function. Clinics in perinatology. 1992 Mar;19:33-57.
28.Alcorn J, McNamara PJ. Ontogeny of hepatic and renal systemic clearance pathways in infants: part I. Clinical pharmacokinetics. 2002;41:959-98.
29.Alcorn J, McNamara PJ. Ontogeny of hepatic and renal systemic clearance pathways in infants: part II. Clinical pharmacokinetics. 2002;41:1077-94.
30.Hayton WL. Maturation and growth of renal function: dosing renally cleared drugs in children. AAPS pharmSci. 2000;2:E3.
31.Hayton WL, Kneer J, de Groot R, Stoeckel K. Influence of maturation and growth on cefetamet pivoxil pharmacokinetics: rational dosing for infants. Antimicrobial agents and chemotherapy. 1996 Mar;40:567-74.
32.Kee J, Marshall S. Calculations for specialty areas. In: Clinical calculations: with applications to general and specialty areas 7th ed St Louis: Elseviers (Saunders). 2012:240-69.
33.Boxenbaum H. Interspecies pharmacokinetic scaling and the evolutionary-comparative paradigm. Drug metabolism reviews. 1984;15:1071-121.
34.Mahmood I. Introduction to allometry. In: Interspecies pharmacokinetic scaling: principles and application of allometric scaling. Rockville: Pine House Publishers. 2012:41-55.
35.Kleiber M. Body size and metabolic rate. Physiological reviews. 1947 Oct;27:511-41.
36.Stahl WR. Scaling of respiratory variables in mammals. Journal of applied physiology. 1967 Mar;22:453-60.
37.Hu TM, Hayton WL. Allometric scaling of xenobiotic clearance: uncertainty versus universality. AAPS pharmSci. 2001;3:E29.
38.Hu TM, & Chiu, S. J. Prediction of human drug clearance using a single-species, fixed-exponent allometric approach. Journal of Medical Sciences (Taiwan). 2009;29:331-9.
39.施懿芸: 小兒嗎啡清除率預測模型的建立以及不同預測方法的比較. 國防醫學院藥學研究所碩士論文, 2014: p. 1-103.
40.McMahon T. Size and shape in biology. Science (New York, NY). 1973 Mar 23;179:1201-4.
41.West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science (New York, NY). 1997 Apr 04;276:122-6.
42.West GB, Brown JH, Enquist BJ. The fourth dimension of life: fractal geometry and allometric scaling of organisms. Science (New York, NY). 1999 Jun 04;284:1677-9.
43.White CR, Cassey P, Blackburn TM. Allometric exponents do not support a universal metabolic allometry. Ecology. 2007 Feb;88:315-23.
44.McLeay SC, Morrish GA, Kirkpatrick CM, Green B. The relationship between drug clearance and body size: systematic review and meta-analysis of the literature published from 2000 to 2007. Clinical pharmacokinetics. 2012 May 01;51:319-30.
45.Mahmood I. Dosing in children: a critical review of the pharmacokinetic allometric scaling and modelling approaches in paediatric drug development and clinical settings. Clinical pharmacokinetics. 2014 Apr;53:327-46.
46.Ding J, Wang Y, Lin W, Wang C, Zhao L, Li X, et al. A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation. Clinical pharmacokinetics. 2015 Mar;54:305-17.
47.Mahmood I, Staschen CM, Goteti K. Prediction of drug clearance in children: an evaluation of the predictive performance of several models. The AAPS journal. 2014 Nov;16:1334-43.
48.Johnson TN, Rostami-Hodjegan A, Tucker GT. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clinical pharmacokinetics. 2006;45:931-56.
49.Mahmood I, Staschen CM. Prediction of Human Glomerular Filtration Rate from Preterm Neonates to Adults: Evaluation of Predictive Performance of Several Empirical Models. The AAPS journal. 2016 Mar;18:445-54.
50.Chan LM, Lowes S, Hirst BH. The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2004 Jan;21:25-51.
51.van Kalken CK, Giaccone G, van der Valk P, Kuiper CM, Hadisaputro MM, Bosma SA, et al. Multidrug resistance gene (P-glycoprotein) expression in the human fetus. The American journal of pathology. 1992 Nov;141:1063-72.
52.Chen HL, Chen HL, Liu YJ, Feng CH, Wu CY, Shyu MK, et al. Developmental expression of canalicular transporter genes in human liver. Journal of hepatology. 2005 Sep;43:472-7.
53.Johnson TN. Modelling approaches to dose estimation in children. British journal of clinical pharmacology. 2005 Jun;59:663-9.
54.Johnson TN. The problems in scaling adult drug doses to children. Archives of disease in childhood. 2008 Mar;93:207-11.
55.Edginton AN, Schmitt W, Voith B, Willmann S. A mechanistic approach for the scaling of clearance in children. Clinical pharmacokinetics. 2006;45:683-704.
56.Anderson BJ, Holford NH. Mechanistic basis of using body size and maturation to predict clearance in humans. Drug metabolism and pharmacokinetics. 2009;24:25-36.
57.Holford N, Heo YA, Anderson B. A pharmacokinetic standard for babies and adults. Journal of pharmaceutical sciences. 2013 Sep;102:2941-52.
58.Ivanchuk SM, Eng C, Cavenee WK, Mulligan LM. The expression of RET and its multiple splice forms in developing human kidney. Oncogene. 1997 Apr 17;14:1811-8.
59.Allegaert K, Anderson BJ, Verbesselt R, Debeer A, de Hoon J, Devlieger H, et al. Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P-450 2D6 activity. British journal of anaesthesia. 2005 Aug;95:231-9.
60.Engle WA. Age terminology during the perinatal period. Pediatrics. 2004 Nov;114:1362-4.
61.Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatric nephrology (Berlin, Germany). 2009 Jan;24:67-76.
62.Germovsek E, Barker CI, Sharland M, Standing JF. Scaling clearance in paediatric pharmacokinetics: All models are wrong, which are useful? British journal of clinical pharmacology. 2017 Apr;83:777-90.
63.De Cock RF, Piana C, Krekels EH, Danhof M, Allegaert K, Knibbe CA. The role of population PK-PD modelling in paediatric clinical research. European journal of clinical pharmacology. 2011 May;67 Suppl 1:5-16.
64.Zhou W, Johnson TN, Xu H, Cheung S, Bui KH, Li J, et al. Predictive Performance of Physiologically Based Pharmacokinetic and Population Pharmacokinetic Modeling of Renally Cleared Drugs in Children. CPT: pharmacometrics & systems pharmacology. 2016 Sep;5:475-83.
65.Jiang XL, Zhao P, Barrett JS, Lesko LJ, Schmidt S. Application of physiologically based pharmacokinetic modeling to predict acetaminophen metabolism and pharmacokinetics in children. CPT: pharmacometrics & systems pharmacology. 2013 Oct 16;2:e80.
66.De Cock RF, Allegaert K, Schreuder MF, Sherwin CM, de Hoog M, van den Anker JN, et al. Maturation of the glomerular filtration rate in neonates, as reflected by amikacin clearance. Clinical pharmacokinetics. 2012 Feb 01;51:105-17.
67.Lanao JM, Calvo MV, Mesa JA, Martin-Suarez A, Carbajosa MT, Miguelez F, et al. Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates. The Journal of antimicrobial chemotherapy. 2004 Jul;54:193-8.
68.Anderson BJ, Allegaert K, Van den Anker JN, Cossey V, Holford NH. Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance. British journal of clinical pharmacology. 2007 Jan;63:75-84.
69.Kimura T, Sunakawa K, Matsuura N, Kubo H, Shimada S, Yago K. Population pharmacokinetics of arbekacin, vancomycin, and panipenem in neonates. Antimicrobial agents and chemotherapy. 2004 Apr;48:1159-67.
70.Robbie GJ, Zhao L, Mondick J, Losonsky G, Roskos LK. Population pharmacokinetics of palivizumab, a humanized anti-respiratory syncytial virus monoclonal antibody, in adults and children. Antimicrobial agents and chemotherapy. 2012 Sep;56:4927-36.
71.Savic RM, Cowan MJ, Dvorak CC, Pai SY, Pereira L, Bartelink IH, et al. Effect of weight and maturation on busulfan clearance in infants and small children undergoing hematopoietic cell transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2013 Nov;19:1608-14.
72.Foissac F, Bouazza N, Valade E, De Sousa Mendes M, Fauchet F, Benaboud S, et al. Prediction of drug clearance in children. Journal of clinical pharmacology. 2015 Jul;55:739-47.
73.Wang C, Peeters MY, Allegaert K, Blusse van Oud-Alblas HJ, Krekels EH, Tibboel D, et al. A bodyweight-dependent allometric exponent for scaling clearance across the human life-span. Pharmaceutical research. 2012 Jun;29:1570-81.
74.Ince I, de Wildt SN, Wang C, Peeters MY, Burggraaf J, Jacqz-Aigrain E, et al. A novel maturation function for clearance of the cytochrome P450 3A substrate midazolam from preterm neonates to adults. Clinical pharmacokinetics. 2013 Jul;52:555-65.
75.Wang C, Sadhavisvam S, Krekels EH, Dahan A, Tibboel D, Danhof M, et al. Developmental changes in morphine clearance across the entire paediatric age range are best described by a bodyweight-dependent exponent model. Clinical drug investigation. 2013 Jul;33:523-34.
76.Walther. BA, Moore. JL. The concepts of bias, precision and accuracy, and their use in testing the performance of species richness estimators, with a literature review of estimator performance. Ecography. 2005;28:815-29.
77.Vargus-Adams JN, McMahon MA, Michaud LJ, Bean J, Vinks AA. Pharmacokinetics of amantadine in children with impaired consciousness due to acquired brain injury: preliminary findings using a sparse-sampling technique. PM & R : the journal of injury, function, and rehabilitation. 2010 Jan;2:37-42.
78.Vogelstein B, Kowarski A, Lietman PS. The pharmacokinetics of amikacin in children. The Journal of pediatrics. 1977 Aug;91:333-9.
79.Lanao JM, Dominguez-Gil A, Dominguez-Gil AA, Malaga S, Crespo M, Nuno F. Modification in the pharmacokinetics of amikacin during development. European journal of clinical pharmacology. 1982;23:155-60.
80.Sardemann H, Colding H, Hendel J, Kampmann JP, Hvidberg EF, Vejlsgaard R. Kinetics and dose calculations of amikacin in the newborn. Clinical pharmacology and therapeutics. 1976 Jul;20:59-66.
81.van Niekerk CH, van den Ende J, Hundt HK, Louw EA. Pharmacokinetic study of a paediatric formulation of amoxycillin and clavulanic acid in children. European journal of clinical pharmacology. 1985;29:235-9.
82.Suzuki K, Tanikawa K, Matsuzaki T. Pharmacokinetics and dosing of arbekacin in preterm and term newborn infants. Pediatrics international : official journal of the Japan Pediatric Society. 2003 Apr;45:175-9.
83.Heimann G. Pharmacokinetics and clinical aspects of azlocillin in paediatrics. The Journal of antimicrobial chemotherapy. 1983 May;11 Suppl B:127-35.
84.He Y, Brunstrom-Hernandez JE, Thio LL, Lackey S, Gaebler-Spira D, Kuroda MM, et al. Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy. The Journal of pediatrics. 2014 May;164:1181-8.e8.
85.Wiersma HE, van Boxtel CJ, Butter JJ, van Aalderen WM, Omari T, Benninga MA. Pharmacokinetics of a single oral dose of baclofen in pediatric patients with gastroesophageal reflux disease. Therapeutic drug monitoring. 2003 Feb;25:93-8.
86.Mahmood I. Prediction of Drug Clearance in Premature and Mature Neonates, Infants, and Children 87.Veal GJ, Errington J, Hayden J, Hobin D, Murphy D, Dommett RM, et al. Carboplatin therapeutic monitoring in preterm and full-term neonates. European journal of cancer (Oxford, England : 1990). 2015 Sep;51:2022-30.
88.Veal GJ, Cole M, Errington J, Pearson AD, Gerrard M, Whyman G, et al. Pharmacokinetics of carboplatin and etoposide in infant neuroblastoma patients. Cancer chemotherapy and pharmacology. 2010 May;65:1057-66.
89.Deguchi Y, Koshida R, Nakashima E, Watanabe R, Taniguchi N, Ichimura F, et al. Interindividual changes in volume of distribution of cefazolin in newborn infants and its prediction based on physiological pharmacokinetic concepts. Journal of pharmaceutical sciences. 1988 Aug;77:674-8.
90.Reed MD, Yamashita TS, Knupp CK, Veazey JM, Jr., Blumer JL. Pharmacokinetics of intravenously and intramuscularly administered cefepime in infants and children. Antimicrobial agents and chemotherapy. 1997 Aug;41:1783-7.
91.Mahmood I. Prediction of drug clearance in children from adults: a comparison of several allometric methods. British journal of clinical pharmacology. 2006 May;61:545-57.
92.Mahmood I. Prediction of drug clearance in children: impact of allometric exponents, body weight, and age. Therapeutic drug monitoring. 2007 Jun;29:271-8.
93.McCracken GH, Jr., Threlkeld N, Thomas ML. Pharmacokinetics of ceftazidime in newborn infants. Antimicrobial agents and chemotherapy. 1984 Oct;26:583-4.
94.van den Anker JN, Schoemaker RC, Hop WC, van der Heijden BJ, Weber A, Sauer PJ, et al. Ceftazidime pharmacokinetics in preterm infants: effects of renal function and gestational age. Clinical pharmacology and therapeutics. 1995 Dec;58:650-9.
95.Autmizguine J, Watt KM, Theoret Y, Kassir N, Laferriere C, Parent S, et al. Pharmacokinetics and pharmacodynamics of oral cephalexin in children with osteoarticular infections. The Pediatric infectious disease journal. 2013 Dec;32:1340-4.
96.Caruso Brown AE, Cohen MN, Tong S, Braverman RS, Rooney JF, Giller R, et al. Pharmacokinetics and safety of intravenous cidofovir for life-threatening viral infections in pediatric hematopoietic stem cell transplant recipients. Antimicrobial agents and chemotherapy. 2015 Jul;59:3718-25.
97.Somogyi A, Becker M, Gugler R. Cimetidine pharmacokinetics and dosage requirements in children. European journal of pediatrics. 1985 May;144:72-6.
98.Lloyd CW, Martin WJ, Taylor BD, Hauser AR. Pharmacokinetics and pharmacodynamics of cimetidine and metabolites in critically ill children. The Journal of pediatrics. 1985 Aug;107:295-300.
99.James LP, Marshall JD, Heulitt MJ, Wells TG, Letzig L, Kearns GL. Pharmacokinetics and pharmacodynamics of famotidine in children. Journal of clinical pharmacology. 1996 Jan;36:48-54.
100. James LP, Marotti T, Stowe CD, Farrar HC, Taylor BJ, Kearns GL. Pharmacokinetics and pharmacodynamics of famotidine in infants. Journal of clinical pharmacology. 1998 Dec;38:1089-95.
101. Saxen H, Hoppu K, Pohjavuori M. Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life. Clinical pharmacology and therapeutics. 1993 Sep;54:269-77.
102. Nahata MC, Brady MT. Pharmacokinetics of fluconazole after oral administration in children with human immunodeficiency virus infection. European journal of clinical pharmacology. 1995;48:291-3.
103. Vert P, Broquaire M, Legagneur M, Morselli PL. Pharmacokinetics of furosemide in neonates. European journal of clinical pharmacology. 1982;22:39-45.
104. Tuck S, Morselli P, Broquaire M, Vert P. Plasma and urinary kinetics of furosemide in newborn infants. The Journal of pediatrics. 1983 Sep;103:481-5.
105. Edginton AN, Shah B, Sevestre M, Momper JD. The integration of allometry and virtual populations to predict clearance and clearance variability in pediatric populations over the age of 6 years. Clinical pharmacokinetics. 2013 Aug;52:693-703.
106. Zhang D, Lapeyraque AL, Popon M, Loirat C, Jacqz-Aigrain E. Pharmacokinetics of ganciclovir in pediatric renal transplant recipients. Pediatric nephrology (Berlin, Germany). 2003 Sep;18:943-8.
107. Capparelli EV, Reed MD, Bradley JS, Kearns GL, Jacobs RF, Damle BD, et al. Pharmacokinetics of gatifloxacin in infants and children. Antimicrobial agents and chemotherapy. 2005 Mar;49:1106-12.
108. Pons G, d'Athis P, Rey E, de Lauture D, Richard MO, Badoual J, et al. Gentamicin monitoring in neonates. Therapeutic drug monitoring. 1988;10:421-7.
109. Tod M, Padoin C, Petitjean O. Clinical pharmacokinetics and pharmacodynamics of isepamicin. Clinical pharmacokinetics. 2000 Mar;38:205-23.
110. Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3-<36 months. Antiviral therapy. 2010;15:297-305.
111. Bergshoeff A, Burger D, Verweij C, Farrelly L, Flynn J, Le Prevost M, et al. Plasma pharmacokinetics of once- versus twice-daily lamivudine and abacavir: simplification of combination treatment in HIV-1-infected children (PENTA-13). Antiviral therapy. 2005;10:239-46.
112. Chien S, Wells TG, Blumer JL, Kearns GL, Bradley JS, Bocchini JA, Jr., et al. Levofloxacin pharmacokinetics in children. Journal of clinical pharmacology. 2005 Feb;45:153-60.
113. Edginton AN, Schmitt W, Willmann S. Development and evaluation of a generic physiologically based pharmacokinetic model for children. Clinical pharmacokinetics. 2006;45:1013-34.
114. Hogg RJ, Delucchi A, Sakihara G, Wells TG, Tenney F, Batisky DL, et al. A multicenter study of the pharmacokinetics of lisinopril in pediatric patients with hypertension. Pediatric nephrology (Berlin, Germany). 2007 May;22:695-701.
115. Vitiello B, Behar D, Malone R, Delaney MA, Ryan PJ, Simpson GM. Pharmacokinetics of lithium carbonate in children. Journal of clinical psychopharmacology. 1988 Oct;8:355-9.
116. van Enk JG, Touw DJ, Lafeber HN. Pharmacokinetics of meropenem in preterm neonates. Therapeutic drug monitoring. 2001 Jun;23:198-201.
117. Blumer JL, Reed MD, Kearns GL, Jacobs RF, Gooch WM, 3rd, Yogev R, et al. Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children. Antimicrobial agents and chemotherapy. 1995 Aug;39:1721-5.
118. Sanchez-Infantes D, Diaz M, Lopez-Bermejo A, Marcos MV, de Zegher F, Ibanez L. Pharmacokinetics of metformin in girls aged 9 years. Clinical pharmacokinetics. 2011 Nov 01;50:735-8.
119. Donelli MG, Zucchetti M, Robatto A, Perlangeli V, D'Incalci M, Masera G, et al. Pharmacokinetics of HD-MTX in infants, children, and adolescents with non-B acute lymphoblastic leukemia. Medical and pediatric oncology. 1995 Mar;24:154-9.
120. Nahata MC, Durrell DE, Barson WJ. Moxalactam epimer kinetics in children. Clinical pharmacology and therapeutics. 1982 Apr;31:528-32.
121. Mahmood I. Interspecies scaling for the prediction of drug clearance in children: application of maximum lifespan potential and an empirical correction factor. Clinical pharmacokinetics. 2010 Jul;49:479-92.
122. Kuhn RJ, Nahata MC, Powell DA, Bickers RG. Pharmacokinetics of netilmicin in premature infants. European journal of clinical pharmacology. 1986;29:635-7.
123. Abdel-Rahman SM, Johnson FK, Connor JD, Staiano A, Dupont C, Tolia V, et al. Developmental pharmacokinetics and pharmacodynamics of nizatidine. Journal of pediatric gastroenterology and nutrition. 2004 Apr;38:442-51.
124. Abdel-Rahman SM, Johnson FK, Manowitz N, Holmes GB, Kearns GL. Single-dose pharmacokinetics of nizatidine (Axid) in children. Journal of clinical pharmacology. 2002 Oct;42:1089-96.
125. Kimberlin DW, Acosta EP, Prichard MN, Sanchez PJ, Ampofo K, Lang D, et al. Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza. The Journal of infectious diseases. 2013 Mar 01;207:709-20.
126. Oo C, Hill G, Dorr A, Liu B, Boellner S, Ward P. Pharmacokinetics of anti-influenza prodrug oseltamivir in children aged 1-5 years. European journal of clinical pharmacology. 2003 Sep;59:411-5.
127. Meistelman C, Agoston S, Kersten UW, Saint-Maurice C, Bencini AF, Loose JP. Pharmacokinetics and pharmacodynamics of vecuronium and pancuronium in anesthetized children. Anesthesia and analgesia. 1986 Dec;65:1319-23.
128. Wilson CB, Koup JR, Opheim KE, Adelman LA, Levy J, Stull TL, et al. Piperacillin pharmacokinetics in pediatric patients. Antimicrobial agents and chemotherapy. 1982 Sep;22:442-7.
129. Moffett BS, Cannon BC, Friedman RA, Kertesz NJ. Therapeutic levels of intravenous procainamide in neonates: a retrospective assessment. Pharmacotherapy. 2006 Dec;26:1687-93.
130. Nelson JD, Kusmiesz H, Shelton S, Woodman E. Clinical pharmacology and efficacy of ticarcillin in infants and children. Pediatrics. 1978 Jun;61:858-63.
131. Nelson JD, Shelton S, Kusmiesz H. Clinical pharmacology of ticarcillin in the newborn infant: relation to age, gestational age, and weight. The Journal of pediatrics. 1975 Sep;87:474-9.
132. Jacobs RF, Trang JM, Kearns GL, Warren RH, Brown AL, Underwood FL, et al. Ticarcillin/clavulanic acid pharmacokinetics in children and young adults with cystic fibrosis. The Journal of pediatrics. 1985 Jun;106:1001-7.
133. Nahata MC, Powell DA, Durrell DE, Miller MA. Tobramycin pharmacokinetics in very low birth weight infants. British journal of clinical pharmacology. 1986 Mar;21:325-7.
134. Battino D, Croci D, Rossini A, Messina S, Mamoli D, Perucca E. Topiramate pharmacokinetics in children and adults with epilepsy: a case-matched comparison based on therapeutic drug monitoring data. Clinical pharmacokinetics. 2005;44:407-16.
135. Lisby-Sutch SM, Nahata MC. Dosage guidelines for the use of vancomycin based on its pharmacokinetics in infants. European journal of clinical pharmacology. 1988;35:637-42.
136. Jarrett RV, Marinkovich GA, Gayle EL, Bass JW. Individualized pharmacokinetic profiles to compute vancomycin dosage and dosing interval in preterm infants. The Pediatric infectious disease journal. 1993 Feb;12:156-7.
137. Schaad UB, McCracken GH, Jr., Nelson JD. Clinical pharmacology and efficacy of vancomycin in pediatric patients. The Journal of pediatrics. 1980 Jan;96:119-26.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔