Tissue distribution, subcellular localization and covalent binding of 2-chloroaniline and 4-chloroaniline in Fischer 344 rats

Dial, Larry; Anestis, Dianne K.; Kennedy, Stephen R.; Rankin, Gary O.

doi:10.1016/s0300-483x(98)00122-x

Cited by 16 publications

(8 citation statements)

References 25 publications

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“…PAP is a nephrotoxicant in the rat, which has been shown to produce selective necrosis to renal proximal tubules . The model compounds were reported to be mainly eliminated via liver metabolism, rapidly absorbed from the small intestine, and passively permeated through tissue and cellular membranes with no known transporter …”

Section: Methodsmentioning

confidence: 99%

“…The physicochemical parameters such as p K a and log P values, which are necessary for the prediction of tissue to plasma partition coefficients, were taken from literature . This group of small molecule compounds (p K a = 4–5) are soluble in aqueous media and rapidly absorbed, hence, at low doses in humans, they are expected to have complete absorption following oral administration.…”

Section: Methodsmentioning

confidence: 99%

“…The physicochemical parameters such as pKa and log P values, which are necessary for the prediction of tissue to plasma partition coefficients, were taken from literature. [39][40][41][42][43] This group of small molecule compounds (pKa = 4-5) are soluble in aqueous media and rapidly absorbed, [26][27][28][29] hence, at low doses in humans, they are expected to have complete absorption following oral administration. In order to predict the venous blood drug concentration leaving a tissue, the partition coefficient of drug between the tissue and blood (K pu ) needs to be estimated.…”

Section: Pbpk-model Parameter Estimationmentioning

confidence: 99%

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A Novel Method for Assessing Drug Degradation Product Safety Using Physiologically-Based Pharmacokinetic Models and Stochastic Risk Assessment

Nguyen

Stamatis

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2015

Journal of Pharmaceutical Sciences

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Pbpk-model Parameter Estimationmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Method for Assessing Drug Degradation Product Safety Using Physiologically-Based Pharmacokinetic Models and Stochastic Risk Assessment

Nguyen

Stamatis

Kirsch

2015

Journal of Pharmaceutical Sciences

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“…Die unterschiedliche Wirksamkeit von o-und p-Chloranilin wird auf toxikokinetische Ursachen zurückgeführt. o-Chloranilin -mit freier para-Stellung -wird schneller ausgeschieden und bindet weniger an Proteine in Leber und Niere als das wirksamere para-Isomer (Dial et al 1998). …”

Section: Der Einfluss Der Stellungsisomerieunclassified

Monozyklische aromatische Amino‐ und Nitroverbindungen [MAK Value Documentation in German language, 2003]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 37. Lieferung, Ausgabe 2003 Der Artikel enthält folgende Kapitel: Einleitung Einstufung Toxizität Hinweise auf nicht‐genotoxische Effekte Genotoxizität In vitro In vivo Tumorentstehung Wirksamkeit Diskussion Wirkungsmechanismus Struktur‐Wirkungs‐Beziehungen Der Einfluss der Stellungsisomerie Analogien zwischen Arylaminen und Nitroverbindungen Die Gemeinsamkeiten Die Unterschiede Folgerungen für die Einstufung Schlussfolgerungen Ausblick

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“…More than 90% of PCA was excreted into the urine (18,122). Very little PCA was eliminated unchanged and no p-chloroacetanilide was observed.…”

Section: Figure 18-blood Concentration Time Profiles Of Aniline Admimentioning

confidence: 99%

Risk assessment for drug degradation products using physiologically-based pharmacokinetic models

Nguyen¹

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ii To my parents and my beloved family, Trung Nguyen, Tri Nguyen and San Nguyen iii The purpose of models is not to fit the data, but to sharpen the questions.Samuel Karlin (1924 ), Evolutionary Geneticist iv ACKNOWLEDGMENTS I would like to express my gratitude to all those people who have made this dissertation possible and because of whom my graduate experience at the University of Iowa has been one that I will cherish forever. This thesis would not have been completed without the help, support and patience of my major advisor, Dr. Lee E. Kirsch. His insightful advices and constructive criticisms at different stages of my research helped me define research scope and develop the ideas. I am grateful to him for assisting me in my growth, and teaching me how to do research. A special thanks goes to Dr. Stephen Stamatis, who has been an invaluable help and enthusiastic mentor, teaching me everything I know about R and programming. He also provided me detailed discussions on PBPK modeling theory. In many ways I have learnt much from and because of him! I also acknowledge Dr. Donovan, former Division Head, who always supports and provides valuable suggestions to students in the department. I would like to thank Dr. Salem, Dr. Jonathan and Dr. Murry for serving on my comprehensive and thesis committee. I am greatly appreciative of all of the professors in the pharmaceutics department who worked with me or taught my courses. In my daily work I enjoyed the academic life with a friendly and cheerful group of fellow students, Mai, Yingjian, Radaduen, Ana, Varsha and Rakesh. I would like to thank them for our exchanges of knowledge, skills and some good laughs. I am also grateful to my former lab mates, Salil, Zong and Jiang whose many informal discussions and guidance were valuable for my progress at the University of Iowa. They are such kind and supportive friends that have helped me overcome setbacks and stay sane through these difficult years. Lastly, I want to thank Prof. Long Nguyen, Prof. Linh Tran and my colleagues at Hanoi University of Pharmacy who encouraged me to continue on academic path. My years at Iowa could not have been memorable without my friends Dan, Linh, Hung, Viet, v Cuong and Hang. Above all, none of this would have been possible without the love and encouragement of my family. My late parents, even without their presence, always cared and stood by me. My husband, with his constant source of love, was always there to cheer me up, supported me through the good and bad times. Words cannot express my love for my children, Tri and San, who are the motivation and joy of my life. vi ABSTRACTDegradation product toxicity is a critical quality issue for a small group of useful drug products-e.g. lidocaine, isoniazid, chlorhexidine, gabapentin. In the traditional risk assessment approaches, a no-observed-adverse-effect level (NOAEL) derived from animal data is determined with the use of generic (and arbitrary) uncertainty factors to obtain an

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Tissue distribution, subcellular localization and covalent binding of 2-chloroaniline and 4-chloroaniline in Fischer 344 rats

Cited by 16 publications

References 25 publications

A Novel Method for Assessing Drug Degradation Product Safety Using Physiologically-Based Pharmacokinetic Models and Stochastic Risk Assessment

A Novel Method for Assessing Drug Degradation Product Safety Using Physiologically-Based Pharmacokinetic Models and Stochastic Risk Assessment

Monozyklische aromatische Amino‐ und Nitroverbindungen [MAK Value Documentation in German language, 2003]

Risk assessment for drug degradation products using physiologically-based pharmacokinetic models

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