Microcomputer Programs For Physiologically Based Pharmacokinetic Pb Pk Modeling

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Microcomputer Programs For Physiologically Based Pharmacokinetic Pb Pk Modeling

Microcomputer Programs For Physiologically Based Pharmacokinetic Pb Pk Modeling written by Michael H. Dong and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1991 with Biological control systems categories.

Documentation Abstracts

Documentation Abstracts written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1994 with Documentation categories.

Dissertation Abstracts International

Dissertation Abstracts International written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1993 with Dissertations, Academic categories.

Government Reports Annual Index

Government Reports Annual Index written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1991 with Government publications categories.

A Comparison Of Physiologically Based Pharmacokinetic Pbpk Models Of Methyl Tertiary Butyl Ether Mtbe

A Comparison Of Physiologically Based Pharmacokinetic Pbpk Models Of Methyl Tertiary Butyl Ether Mtbe written by Nikki Shavon Smith and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.

A Parameter Analysis Of A Physiologically Based Pharmacokinetic Pbpk Model Describing The Movements Of 2 3 7 8 Tetrachlorodibenzo P Dioxin In The Mouse

A Parameter Analysis Of A Physiologically Based Pharmacokinetic Pbpk Model Describing The Movements Of 2 3 7 8 Tetrachlorodibenzo P Dioxin In The Mouse written by Jessica Leigh Wagner and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.

Physiologically Based Pharmacokinetic Pbpk Models For The Description Of Sequential Metabolism Of Codeine To Morphine And Morphine 3 Glucuronide M3g In Man And Rat

Physiologically Based Pharmacokinetic Pbpk Models For The Description Of Sequential Metabolism Of Codeine To Morphine And Morphine 3 Glucuronide M3g In Man And Rat written by Shu Chen and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.

Whole-body PBPK models were developed based on both the intestinal traditional model (TM) and segregated-flow model (SFM) to describe codeine sequential metabolism in man/rat. Model parameters were optimized with ScientistRTM and SimcypRTM simulator to predict literature data after oral (p.o.) and intravenous (i.v.) codeine administration in man/rat. In vivo codeine PK studies on rats were performed to provide more data for simulation. The role of fm' (fractional formation clearance of morphine from codeine) in model discrimination between the TM and SFM was investigated. A greater difference between the [AUC M3G/AUCMorphine]p.o. and [ AUCM3G/AUCMorphine]i.v. ratio existed for the SFM, especially when the fm' was low. It was found that our tailor-made PBPK models using ScientistRTM were superior to those from SimcypRTM in describing codeine sequential metabolism. Residual sum of squares and AUC's were calculated for each model, which demonstrated superiority of the SFM over TM in predicting codeine sequential metabolism in man/rat.

Comparing Paediatric Intravenous Phenytoin Doses Using Physiologically Based Pharmacokinetic Pbpk Modelling Software

Comparing Paediatric Intravenous Phenytoin Doses Using Physiologically Based Pharmacokinetic Pbpk Modelling Software written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with categories.

Physiologically Based Pharmacokinetic Pb Pk Modeling For Dermal Absorption Of Pesticide Malathion In Man

Physiologically Based Pharmacokinetic Pb Pk Modeling For Dermal Absorption Of Pesticide Malathion In Man written by Michael H. Dong and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1993 with Malathion categories.

Pharmacokinetics And Physiologically Based Pharmacokinetic Modeling Of Xenobiotic Disposition In Special Populations

Pharmacokinetics And Physiologically Based Pharmacokinetic Modeling Of Xenobiotic Disposition In Special Populations written by Jing Jing and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.

Due to the alteration of the physiological functions, the disposition of xenobiotics is often changed under disease conditions and during pregnancy compared with the healthy status. Under disease conditions including chronic kidney disease (CKD) and cancer, altered physiological functions including changes in liver and kidney function have critical impact on the pharmacokinetics of xenobiotics. During pregnancy, the changes in organ blood flow, plasma protein binding and the expression of hepatic drug metabolizing enzymes can also affect the intrinsic capacity of the organ to metabolize and excrete xenobiotic. However, little is known on the disposition of vitamin A and its metabolites including all-trans retinoic acid (atRA) in CKD and cancer patients and the disposition of domoic acid (DA), a shellfish toxin, during pregnancy. The aims of the thesis project is to better characterize the disposition of retinoids in CKD and cancer patients, evaluate the disposition of DA before and during pregnancy in non-human primates and utilize the obtained in vitro and in vivo information to develop physiologically based pharmacokinetic (PBPK) model to simulate the disposition of atRA and DA. To evaluate the disposition of endogenous retinoids and their carrier proteins in CKD patients in comparison to healthy subjects, retinoids and their carrier proteins such as retinol binding protein (RBP4) concentrations in plasma and urine from 55 adult CKD patients and 21 matched healthy subjects were measured. RBP4 and retinol levels were increased approximately 2-fold in patients with CKD. RBP4 renal clearance was higher in patients with CKD than healthy subjects but not associated with estimated glomerular filtration rate (eGFR). Circulating concentrations of atRA increased and concentrations of 13cisRA decreased in subjects with CKD with no change in RA-to-retinol ratio. Increases in circulating retinol, RBP4, and atRA may be due to increased hepatic RBP4 synthesis, retinyl ester hydrolysis, and/or hepatic secretion of RBP4-retinol. To better characterize and understand the disposition of therapeutically administered atRA in healthy and cancer patients in the presence and absence of inhibitors of atRA metabolism, a population based PBPK model of atRA disposition incorporated saturable metabolic clearance of atRA, induction of CYP26A1 by atRA and the absorption and distribution kinetics of atRA was developed and verified using in vitro and in vivo data. The developed model can be used for the interpretation of atRA disposition and efficacy, design of novel dosing strategies, and development of next-generation atRA metabolism inhibitors. To investigate the disposition of DA, toxicokinetics of DA were characterized in female cynomolgus monkeys, following a single 5 μg/kg IV bolus dose and single 0.075 mg/kg and 0.15 mg/kg PO dose before pregnancy. Following IV dosing, DA had a distribution volume of 145 ± 69 ml/kg, systemic clearance of 139 ± 70 ml/hr/kg and elimination half-life of 1.4 ± 1.0 hours. However, following PO dosing, the average terminal half-life of DA was 11± 3.7 hours, indicating that after PO administration DA disposition follows flip-flop kinetics with slow rate-limiting absorption. The absolute bioavailability of DA was 7 ± 4 %. DA was primarily renally eliminated with renal clearance of 104 ± 47 ml/hr/kg. The developed DA PBPK model in monkeys simulated the flip-flop kinetics observed after oral administration and allowed the simulation of urinary excretion and brain and kidney distribution of DA, following IV and PO dosing. DA toxicokinetics were further characterized in monkeys during pregnancy following chronic dose of 0.15 mg/kg/day DA. Decreased AUC of DA and increased DA renal clearance were observed during pregnancy. DA was detected in both plasma and urine samples of delivered infants.