Contribution of different oxazolidinones to the efficacy of novel regimens containing bedaquiline and pretomanid in murine models of TB
|
|
- Anthony Parker
- 5 years ago
- Views:
Transcription
1 Contribution of different oxazolidinones to the efficacy of novel regimens containing bedaquiline and pretomanid in murine models of TB Rokeya Tasneen 1, Fabrice Betoudji 1, Véronique Dartois, Tian Yang 3, Khisimuzi E. Mdluli 3, Eric L. Nuermberger 1 1 Johns Hopkins University School of Medicine, Baltimore, MD, Public Health Research Institute and New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ; 3 Global Alliance for TB Drug Development, New York, NY
2 Unmet need in TB treatment A short-course oral regimen that is active against virtually all circulating strains of DR-TB is safe and well-tolerated has no serious drug-drug interactions produces cure rates at least comparable to the first-line regimen for drug susceptible TB prevents selection of mutants resistant to component drugs
3 Background The novel combo of bedaquiline+pretomanid (JPa) plus sutezolid (U) has sterilizing activity superior to the 1 st -line regimen (RHZ) in BALB/c mice As linezolid (L) & tedizolid (T) are marketed agents, and AZD 57 is in Phase II, these oxies warrant evaluation in this combo. Further study of these combos in C3HeB/FeJ mice which, unlike BALB/c mice, develop caseous lesions will be useful to confirm their efficacy. R Tasneen et al, AAC 15; 59:19
4 Oxazolidinone plasma AUC in BALB/c mice (JHU) and humans, with reference to MIC vs. M. tb Drug Species Dose AUC -h (µg-h/ml) MIC* (µg/ml) Linezolid Mouse 1 mpk.5-1. Human 1 mg 15-9 Sutezolid Mouse 5 mpk Mouse (M1) 5 mpk Human 1 mg 7.13 Human (M1) 1 mpk 3. Tedizolid Mouse 1 mpk..5 mpk 77.7 Human mg - AZD 57 Mouse 15 mpk Human mg bid 1. *MIC 5, geometric mean or median values from the literature
5 Addition of a linezolid (L) or sutezolid (U) increases the bactericidal activity of bedaquiline+pretomanid (JPa) in BALB/c mice weeks Doses tested J = 5 mpk Pa = 1 mpk L = 5-1 mpk U = 5 mpk weeks Lung log 1 CFU Lung log 1 CFU D JPa JPaU JPaL 5 JPaL 1 D RHZ JPa JPaU JPaL 5 1. Both oxies increased the bactericidal activity of the JPa combo.. The JPaOxie combos were superior to RHZ at wks. 3. U was superior to L at either dose.. Halving the L dose or duration did not significantly affect results at weeks. JPaL 1 1JPaL 1, 1JPa
6 Addition of a linezolid (L) or sutezolid (U) increases the sterilizing activity of bedaquiline+pretomanid (JPa) in BALB/c mice Proportion relapsing after treatment for: Regimen months 3 months RHZ/RH /1 (57%) JPa 3/1 (1%) JPaU 1/1 (7%) 3JPaL 1 /15 (%) *p =.11 vs. JPa; p.1 vs. RHZ by 1-tailed Fisher exact test /1* (%) /15* (%) 1. JPaU and JPaL were superior to RHZ at 3 months, but JPa was not. Limiting the duration of L 1 to the first month modestly reduced sterilizing activity
7 L u n g lo g 1 C F U L u n g lo g 1 C F U AZD 57 (AZD) and tedizolid (T) increase the activity of JPa in BALB/c mice, but not as much as U or L w e e k s w e e k s D J P a J P a U J P a L 1 J P a L 5 J P a A Z D J P a T D R H Z J P a J P a U J P a L 1 J P a L 5 J P a A Z D J P a T At wks: all oxies add to JPa except T (p<.1 for U, L, RWJ; p<.5 for AZD) At wks: all oxies add to JPa (p<.1 for U, L, RWJ; p<.1 for AZD; p<.5 for T) Drug doses (in mpk): U 5; L5-1; AZD 15; T 1 (as pro-drug)
8 L u n g lo g 1 C F U L u n g lo g 1 C F U Sutezolid and linezolid increase the bactericidal activity of JPa in C3HeB/FeJ mice w e e k s w e e k s 1 1 D R H Z J P a J P a U J P a L J P a A z D R H Z J P a J P a U J P a L J P a A z At wks: all oxies but AZD add to JPa At wks: no oxie adds to JPa (p<.1)
9 L u n g lo g 1 C F U L o g 1 C F U /L u n g JPa + oxies in C3HeB/FeJ mice, nd expt C o m b o e x p t 1 ( w k s ) D o s e -ra n g in g e x p t ( w k s ) 1 1 D R H Z J P a J P a U J P a L J P a A z D O J P a J P a U J P a L 5 J P a L 5 J P a L 1 J P a A Z D Only U and L1 add to JPa (p<.1 and p<.5) 1. JPaU and JPaL1 were superior to JPa. L had dose-dependent additive effects. At 1 mpk, activity is comparable to U.
10 Tedizolid also has dose-dependent effects in combination with JPa in C3HeB/FeJ mice BALB/c C3HeB/FeJ 1 1 Lung log 1 CFU Log 1 CFU/Lung D JPa JPaL 5 JPaL 1 JPaT1 DO JPa JPaL5 JPaL5 JPaL1 JPaT1 JPaT 1. JPaT was not statistically superior to JPa alone. T at 1 and mpk had effects similar to L at 5 and 5 mpk, respectively
11 L o g 1 C F U /lu n g Sterilizing activity of oxazolidinones in combination with JPa in C3HeB/FeJ Mice (Relapse Expt) 1 Lung CFU counts after months D O R H Z J P a J P a U J P a L Doses (in mpk): U (5), L (1), T () J P a T Relapses after 3 months of treatment % relapsing vs. RHZ vs. JPa Regimen RHZ 91% NA NA JPa % * NA JPaU 7% *** * JPaL 9% ** NS JPaT 1% *** NS *p<.5, **p<.1, ***p<.1 Relapses after.5 months of treatment % relapsing vs. RHZ vs. JPa Regimen RHZ 1% NA NA JPa % NA JPaU % NS JPaL % NS JPaT % NS p=.7 1. JPaOxie combos reduced the treatment duration by ~1.5 months vs. RHZ. Only U added sterilizing activity to the JPa combination in a stat. significant fashion 3. In this nd expt in C3HeB/FeJ mice, T was at least as potent as L1 11
12 Comparative single-dose PK in BALB/c and C3HeB/FeJ mice Table 1, Pharmacokinetic parameters after single dose oral administration of Sutezolid, Linezolid, and Tedizolid in BALB/C mice. Compound (dose, mg/kg) t1/ Tmax Cmax AUC-hr AUC- hr/dose Cavg,-hr hr hr ng/ml hr*ng/ml hr*ng/ml/mg ng/ml Sutezolid Mean SD Sutezolid M1 Mean SD Linezolid Mean SD Tedizolid Mean SD Tedizolid Mean SD Table, Pharmacokinetic parameters after single dose oral administration of Sutezolid, Linezolid, and Tedizolid in Kramnik mice. AUC- Compound t1/ Tmax Cmax AUC-hr hr/dose Cavg, -hr dose, mg/kg hr hr ng/ml hr*ng/ml hr*ng/ml/mg ng/ml Sutezolid Mean SD Sutezolid M1 Mean SD Linezolid Mean SD Tedizolid Mean SD NAME OF PRESENTATION 1
13 Conclusions JPa + an oxazolidinone has potential for short-course oral regimens for all forms of TB, justifying evaluation of JPaL in the Nix-TB trial Sutezolid was the most active oxie in the combo in BALB/c mice, but was not clearly superior to linezolid, tedizolid in C3HeB/FeJ However, the L and T exposures produced in the C3HeB/FeJ relapse expt were higher relative to U than in BALB/c mice, and exceeded the average human exposure at the highest approved doses Additional work is needed to confirm whether lower L and T exposures contribute sterilizing activity in C3HeB/FeJ mice Relapse results after months of treatment may help to understand if early mortality in JPa-containing groups may have biased the efficacy results in their favor
14 Acknowledgements Colleagues Faculty and staff of the JHU Center for TB Research Matt Zimmerman (Rutgers) Colleagues at the TB Alliance Omar Vandal (Gates Foundation) Anne Lenaerts and colleagues (Colorado St.) Funding Gates Foundation (OPP13717 & OPP199) TB Alliance NIAID (R1-AI11199, R1-AI9)
Influence of Bacterial Growth Rate on Dose Optimization of Linezolid for Treatment of Tuberculosis
Influence of Bacterial Growth Rate on Dose Optimization of Linezolid for Treatment of Tuberculosis Kristina Bigelow Johns Hopkins University School of Medicine 1/15/217 Linezolid Recently added to WHOs
More informationAlita Miller, PhD. Head of BioScience. April 24, 2017 ECCMID 2017 Vienna, Austria
ETX5 restoration of sulbactam activity against multidrug resistant Acinetobacter baumannii correlates with β-lactamase inhibition in vitro and in vivo Alita Miller, PhD Head of BioScience April, 07 ECCMID
More informationPK-QT analysis of bedaquiline : Bedaquiline appears to antagonize its main metabolite s QTcF interval prolonging effect
PK-QT analysis of bedaquiline : Bedaquiline appears to antagonize its main metabolite s QTcF interval prolonging effect Lénaïg Tanneau 1, Elin Svensson 1,2, Stefaan Rossenu 3, Mats Karlsson 1 1 Department
More informationValidation of the GastroPlus TM Software Tool and Applications
Validation of the GastroPlus TM Software Tool and Applications Fagen Zhang and Leah Luna The Dow Chemical Company FZ/MB 01.11.11 Acknowledgements Michael Bartels Barun Bhhatarai (Novartis) Tyler Auernhammer
More informationThe general concept of pharmacokinetics
The general concept of pharmacokinetics Hartmut Derendorf, PhD University of Florida Pharmacokinetics the time course of drug and metabolite concentrations in the body Pharmacokinetics helps to optimize
More informationCTP-656 Tablet Confirmed Superiority Of Pharmacokinetic Profile Relative To Kalydeco in Phase I Clinical Studies
Tablet Confirmed Superiority Of Pharmacokinetic Profile Relative To Kalydeco in Phase I Clinical Studies 39 th European Cystic Fibrosis Conference 8-11 June 2016, Basel, Switzerland 2014 Concert Pharmaceuticals,
More informationStudy No: Title : Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Statistical Methods:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationPhase I design for locating schedule-specific maximum tolerated doses
Phase I design for locating schedule-specific maximum tolerated doses Nolan A. Wages, Ph.D. University of Virginia Division of Translational Research & Applied Statistics Department of Public Health Sciences
More informationIVIVC Industry Perspective with Illustrative Examples
IVIVC Industry Perspective with Illustrative Examples Presenter: Rong Li Pfizer Inc., Groton, CT rong.li@pfizer.com 86.686.944 IVIVC definition 1 Definition A predictive mathematical treatment describing
More informationEUCAST. Linezolid Rationale for the EUCAST clinical breakpoints, version th November 2005
Linezolid - Rationale document (http://www.eucast.org) 1 (9) Linezolid Rationale for the clinical breakpoints, version 1.0 18 th November 2005 Introduction Linezolid is the only clinically available representative
More informationSTUDY OF THE APPLICABILTY OF CONTENT UNIFORMITY AND DISSOLUTION VARIATION TEST ON ROPINIROLE HYDROCHLORIDE TABLETS
& STUDY OF THE APPLICABILTY OF CONTENT UNIFORMITY AND DISSOLUTION VARIATION TEST ON ROPINIROLE HYDROCHLORIDE TABLETS Edina Vranić¹*, Alija Uzunović² ¹ Department of Pharmaceutical Technology, Faculty of
More informationSupporting information
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 209 Supporting information Na 2 S promoted reduction of azides in water: Synthesis
More informationInternal dose assessment of 177 Lu-DOTA-SP for quantification of arginine renal protection effect
Internal dose assessment of 177 Lu-DOTA-SP for quantification of arginine renal protection effect 1 Puerta N., 1 Rojo A., 2 Crudo J., 2 Zapata A., 2 Nevares N., 2 López Bularte A., 2 Perez J., 2 Zaretzky
More informationModeling & Simulation to Improve the Design of Clinical Trials
Modeling & Simulation to Improve the Design of Clinical Trials Gary L. Rosner Oncology Biostatistics and Bioinformatics The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Joint work with Lorenzo
More informationHow Critical is the Duration of the Sampling Scheme for the Determination of Half-Life, Characterization of Exposure and Assessment of Bioequivalence?
How Critical is the Duration of the Sampling Scheme for the Determination of Half-Life, Characterization of Exposure and Assessment of Bioequivalence? Philippe Colucci 1,2 ; Jacques Turgeon 1,3 ; and Murray
More informationDesigns for Clinical Trials
Designs for Clinical Trials Chapter 5 Reading Instructions 5.: Introduction 5.: Parallel Group Designs (read) 5.3: Cluster Randomized Designs (less important) 5.4: Crossover Designs (read+copies) 5.5:
More informationHomework 1 (PHA 5127)
Homework 1 (PHA 5127) 1. The elimination rate constant of a drug is 1 hr -1 : k e =1 hr -1 A. Half-life: t 1/2 = ln(2)/k e = 0.693/1 hr -1 = 0.693 hr B. C 1 =5ng/ml First-order elimination: k e = (ln(c
More informationA Clinical Trial Simulation System, Its Applications, and Future Challenges. Peter Westfall, Texas Tech University Kuenhi Tsai, Merck Research Lab
A Clinical Trial Simulation System, Its Applications, and Future Challenges Peter Westfall, Texas Tech University Kuenhi Tsai, Merck Research Lab Acknowledgement Major collaborators Stephan Ogenstand,
More informationOn Assessing Bioequivalence and Interchangeability between Generics Based on Indirect Comparisons
On Assessing Bioequivalence and Interchangeability between Generics Based on Indirect Comparisons Jiayin Zheng 1, Shein-Chung Chow 1 and Mengdie Yuan 2 1 Department of Biostatistics & Bioinformatics, Duke
More information3 Results. Part I. 3.1 Base/primary model
3 Results Part I 3.1 Base/primary model For the development of the base/primary population model the development dataset (for data details see Table 5 and sections 2.1 and 2.2), which included 1256 serum
More informationThe Calculus Behind Generic Drug Equivalence
The Calculus Behind Generic Drug Equivalence Stanley R. Huddy and Michael A. Jones Stanley R. Huddy srh@fdu.edu, MRID183534, ORCID -3-33-231) isanassistantprofessorat Fairleigh Dickinson University in
More informationMATERIAL SAFETY DATA SHEET
MATERIAL SAFETY DATA SHEET S E C T I O N 1 - I D E N T I F I C A T I O N O F P R O D U C T A N D C O M P A N Y Pfizer Inc Pfizer Animal Health 2 3 5 E a s t 4 2 n d S t r e e t N e w Y o r k, N Y 1 0 0
More informationPHA 4123 First Exam Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.
PHA 4123 First Exam Fall 1998 On my honor, I have neither given nor received unauthorized aid in doing this assignment. TYPED KEY Name Question 1. / pts 2. /2 pts 3. / pts 4. / pts. / pts 6. /10 pts 7.
More informationNonlinear pharmacokinetics
5 Nonlinear pharmacokinetics 5 Introduction 33 5 Capacity-limited metabolism 35 53 Estimation of Michaelis Menten parameters(v max andk m ) 37 55 Time to reach a given fraction of steady state 56 Example:
More informationSupplementary Material (ESI) for Natural Product Reports This journal is The Royal Society of Chemistry Effect on promastigotes, amastigotes of
upplementary Material (EI) for atural Product Reports This journal is The Royal ociety of Chemistry 2010 Table 2. Biological activities of purely synthetic guanidines Entry Guanidine compound Biological
More informationCompare Predicted Counts between Groups of Zero Truncated Poisson Regression Model based on Recycled Predictions Method
Compare Predicted Counts between Groups of Zero Truncated Poisson Regression Model based on Recycled Predictions Method Yan Wang 1, Michael Ong 2, Honghu Liu 1,2,3 1 Department of Biostatistics, UCLA School
More informationResults of a simulation of modeling and nonparametric methodology for count data (from patient diary) in drug studies
Results of a simulation of modeling and nonparametric methodology for count data (from patient diary) in drug studies Erhard Quebe-Fehling Workshop Stat. Methoden für korrelierte Daten Bochum 24-Nov-06
More informationModelling a complex input process in a population pharmacokinetic analysis: example of mavoglurant oral absorption in healthy subjects
Modelling a complex input process in a population pharmacokinetic analysis: example of mavoglurant oral absorption in healthy subjects Thierry Wendling Manchester Pharmacy School Novartis Institutes for
More informationThe Longer Life Foundation Pilot/Feasibility Grant Application FINAL REPORT
The Longer Life Foundation Pilot/Feasibility Grant Application FINAL REPORT Diagnostic and therapeutic applications of a novel plasma metabolite, nicotinamide mononucleotide (NMN), for age-associated metabolic
More informationJournal home page:
Page6460 Indo American Journal of Pharmaceutical Research, 2013 ISSN NO: 2231-6876 Journal home page: http:///index.php/en/ INDO AMERICAN JOURNAL OF PHARMACEUTICAL RESEARCH PHASE SOLUBILITY STUDY ON MUSCLE
More informationCompound Optimal Designs for Percentile Estimation in Dose-Response Models with Restricted Design Intervals
Compound Optimal Designs for Percentile Estimation in Dose-Response Models with Restricted Design Intervals Stefanie Biedermann 1, Holger Dette 1, Wei Zhu 2 Abstract In dose-response studies, the dose
More informationDosing In NONMEM Data Sets an Enigma
PharmaSUG 2018 - Paper BB-02 ABSTRACT Dosing In NONMEM Data Sets an Enigma Sree Harsha Sreerama Reddy, Certara, Clarksburg, MD; Vishak Subramoney, Certara, Toronto, ON, Canada; Dosing data plays an integral
More informationMA/ST 810 Mathematical-Statistical Modeling and Analysis of Complex Systems
MA/ST 810 Mathematical-Statistical Modeling and Analysis of Complex Systems Integrating Mathematical and Statistical Models Recap of mathematical models Models and data Statistical models and sources of
More informationThe Bcl3 Story : Collabora2ve Drug Discovery In Ac2on
The Bcl3 Story : Collabora2ve Drug Discovery In Ac2on Dr Andrew Westwell Drug Development & Model Systems Package Lead Dr Luke Piggo> Research Associate, WCRC Rachel Savery Trials Project Manager (Early
More informationComparing Adaptive Interventions Using Data Arising from a SMART: With Application to Autism, ADHD, and Mood Disorders
Comparing Adaptive Interventions Using Data Arising from a SMART: With Application to Autism, ADHD, and Mood Disorders Daniel Almirall, Xi Lu, Connie Kasari, Inbal N-Shani, Univ. of Michigan, Univ. of
More informationAn extrapolation framework to specify requirements for drug development in children
An framework to specify requirements for drug development in children Martin Posch joint work with Gerald Hlavin Franz König Christoph Male Peter Bauer Medical University of Vienna Clinical Trials in Small
More informationCHEM 200 Chapter 2 General Work Practices
1 The cost of laboratory accidents can be enormous in terms of fatalities, serious injuries, property loss, and the costs of replacing equipment and repairing or rebuilding laboratories. For that reason,
More informationFlexible modelling of the cumulative effects of time-varying exposures
Flexible modelling of the cumulative effects of time-varying exposures Applications in environmental, cancer and pharmaco-epidemiology Antonio Gasparrini Department of Medical Statistics London School
More informationSupplementary Figure 1: To test the role of mir-17~92 in orthologous genetic model of ADPKD, we generated Ksp/Cre;Pkd1 F/F (Pkd1-KO) and Ksp/Cre;Pkd1
Supplementary Figure 1: To test the role of mir-17~92 in orthologous genetic model of ADPKD, we generated Ksp/Cre;Pkd1 F/F (Pkd1-KO) and Ksp/Cre;Pkd1 F/F ;mir-17~92 F/F (Pkd1-miR-17~92KO) mice. (A) Q-PCR
More informationPubh 8482: Sequential Analysis
Pubh 8482: Sequential Analysis Joseph S. Koopmeiners Division of Biostatistics University of Minnesota Week 10 Class Summary Last time... We began our discussion of adaptive clinical trials Specifically,
More informationSyntheses and Pharmacokinetics Properties of an Iloperidone. Pharmaceutical Cocrystal
Syntheses and Pharmacokinetics Properties of an Iloperidone Pharmaceutical Cocrystal Ting-Ting Zhang a,b, Hai-Tao Wang a,b, Jiang-Tao Jia c, Xiao-Qiang Cui a,b,*, Qin Li d, Guang-Shan Zhu c,d,** a Department
More informationPathogen Inactivation and Function of Platelets and Red Cells
Pathogen Inactivation and Function of Platelets and Red Cells Dr. Dana Devine Professor of Pathology & Laboratory Medicine UBC Centre for Blood Research Chief Medical and Scientific Officer, Canadian Blood
More informationIntroduction to E&Ls 1
Introduction to E&Ls 1 Overview What industries need to determine E&Ls Define extractables and leachables Basic overview of an E&L study Regulatory landscape 2 A leader in plastics analysis Jordi Labs
More informationBASF Petrochemicals The Heart of Your Products. Istanbul E-CPW/MD Heidrun Goth
Istanbul 30.05.2007 E-CPW/MD Heidrun Goth Plasticizers General Aspects Plasticizers of different structural classes are available The availability of the toxicological data varies The concentration of
More informationCase Study in the Use of Bayesian Hierarchical Modeling and Simulation for Design and Analysis of a Clinical Trial
Case Study in the Use of Bayesian Hierarchical Modeling and Simulation for Design and Analysis of a Clinical Trial William R. Gillespie Pharsight Corporation Cary, North Carolina, USA PAGE 2003 Verona,
More informationCHAPTER 1 Role of Bioanalytical Methods in Drug Discovery and Development
UMMERY The need to develop new analytical methods for assurance of quality, safety and efficacy of drugs and pharmaceuticals is quite important because of their use not only as health care products but
More informationInvolvement of efflux pumps in the resistance to peptidoglycan synthesis
AAC Accepts, published online ahead of print on January 0 Antimicrob. Agents Chemother. doi:0./aac.0- Copyright 0, American Society for Microbiology. All Rights Reserved. Involvement of efflux pumps in
More informationAuthors: Antonella Zanobetti and Joel Schwartz
Title: Mortality Displacement in the Association of Ozone with Mortality: An Analysis of 48 US Cities Authors: Antonella Zanobetti and Joel Schwartz ONLINE DATA SUPPLEMENT Additional Information on Materials
More informationEffect of investigator bias on the significance level of the Wilcoxon rank-sum test
Biostatistics 000, 1, 1,pp. 107 111 Printed in Great Britain Effect of investigator bias on the significance level of the Wilcoxon rank-sum test PAUL DELUCCA Biometrician, Merck & Co., Inc., 1 Walnut Grove
More informationEstimation in Flexible Adaptive Designs
Estimation in Flexible Adaptive Designs Werner Brannath Section of Medical Statistics Core Unit for Medical Statistics and Informatics Medical University of Vienna BBS and EFSPI Scientific Seminar on Adaptive
More informationMODULE 1: MATH BASICS
MATH FUNDAMENTALS MODULE 1: MATH BASICS In the medical world, the most beneficial drug can be rendered worthless or dangerous if the veterinarian or animal health technician does not accurately calculate
More informationMulticompartment Pharmacokinetic Models. Objectives. Multicompartment Models. 26 July Chapter 30 1
Multicompartment Pharmacokinetic Models Objectives To draw schemes and write differential equations for multicompartment models To recognize and use integrated equations to calculate dosage regimens To
More informationStandard Practice for Heat Aging of Plastics Without Load 1
Designation: D 3045 92 (Reapproved 2003) Standard Practice for Heat Aging of Plastics Without Load 1 This standard is issued under the fixed designation D 3045; the number immediately following the designation
More informationThe hazards of chemicals vary widely and appropriate caution must always be used. Every chemical can be hazardous in certain circumstances.
1 The hazards of chemicals vary widely and appropriate caution must always be used. Every chemical can be hazardous in certain circumstances. An understanding of the hazards of chemicals and how they enter
More informationTetracycline Rationale for the EUCAST clinical breakpoints, version th November 2009
Tetracycline Rationale for the EUCAST clinical breakpoints, version 1.0 20 th November 2009 Introduction The natural tetracyclines, including tetracycline, chlortetracycline, oxytetracycline and demethylchlortetracycline
More informationSubstantive Program Modification Form
SOUTH DAKOTA BOARD OF REGENTS ACADEMIC AFFAIRS FORMS Substantive Program Modification Form UNIVERSITY: SDSU CURRENT PROGRAM TITLE: Pharmaceutical Sciences (B.S.) [S.BSPHS.PHS] CIP CODE: 51.001 UNIVERSITY
More informationDescriptive statistics
Patrick Breheny February 6 Patrick Breheny to Biostatistics (171:161) 1/25 Tables and figures Human beings are not good at sifting through large streams of data; we understand data much better when it
More informationRisk Assessment of Staphylococcus aureus and Clostridium perfringens in ready to eat Egg Products
Risk Assessment of Staphylococcus aureus and Clostridium perfringens in ready to eat Egg Products Introduction Egg products refer to products made by adding other types of food or food additives to eggs
More informationBIT TM Detailed Technical Discussion
National Security Solutions BIT TM Detailed Technical Discussion Hydrogen peroxide is a strong oxidizer that is used for high-level disinfection and sterilization. It produces reactive hydroxyl free radicals
More informationBIOS 2041: Introduction to Statistical Methods
BIOS 2041: Introduction to Statistical Methods Abdus S Wahed* *Some of the materials in this chapter has been adapted from Dr. John Wilson s lecture notes for the same course. Chapter 0 2 Chapter 1 Introduction
More information5.Experimental Results Table 5.1 Calibration curve for the estimation of Ciprofloxacin. Sl.No. Conc.(μg/ml) Absorbance(nm)
121 5.Experimental Results Table 5.1 Calibration curve for the estimation of Ciprofloxacin Sl.No. Conc.(μg/ml) Absorbance(nm) 1. 2. 3. 4. 5. 6. 10 12 14 16 18 20 0.102 0.280 0.420 0.651 0.840 1.092 Graph5.1
More informationOral Ciprofloxacin Treatment for Salmonella typhimurium Infection of Normal and Immunocompromised Mice
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Jan. 1988, p. 57-62 0066-4804/88/010057-06$02.00/0 Copyright 1988, American Society for Microbiology Vol. 32, No. 1 Oral Ciprofloxacin Treatment for Salmonella typhimurium
More informationSCHOOL OF MATHEMATICS AND STATISTICS. Bayesian Methods and Clinical Trials
Data provided: Tables of distributions and table of Normal Quantiles MAS606 SCHOOL OF MATHEMATICS AND STATISTICS Bayesian Methods and Clinical Trials Spring Semester 014 015 3 hours Candidates may bring
More informationMcGill University. Faculty of Science MATH 204 PRINCIPLES OF STATISTICS II. Final Examination
McGill University Faculty of Science MATH 204 PRINCIPLES OF STATISTICS II Final Examination Date: 23rd April 2007 Time: 2pm-5pm Examiner: Dr. David A. Stephens Associate Examiner: Dr. Russell Steele Please
More informationImproving a safety of the Continual Reassessment Method via a modified allocation rule
Improving a safety of the Continual Reassessment Method via a modified allocation rule Pavel Mozgunov, Thomas Jaki Medical and Pharmaceutical Statistics Research Unit, Department of Mathematics and Statistics,
More informationMEDICAL MATH. Help for the Mathematically Challenged
MEDICAL MATH Help for the Mathematically Challenged The Metric Basics Set up on a scale of ten All units use the same scale Meter = distance Liter = volume Gram = weight For Our Purposes One cubic centimeter
More informationPlant Stress and Phytophthora ramorum Infection
Plant Stress and Phytophthora ramorum Infection Dr. Rick Bostock Department of Plant Pathology University of California, Davis COMTF Annual Meeting June 8-11, 2010 Root stress predisposition to Phytophthora
More informationREVIEW ON APPLICATION OF IBUPROFEN PEDIATRIC SUSPENSION FOR INCLUSION IN WHO MODEL LIST 2005
1 REVIEW ON APPLICATION OF IBUPROFEN PEDIATRIC SUSPENSION FOR INCLUSION IN WHO MODEL LIST 2005 An application has been submitted by the International Ibuprofen Foundation. The application is based on the
More informationGentamicin Rationale for the EUCAST clinical breakpoints, version th February, 2009
Gentamicin Rationale for the EUCAST clinical breakpoints, version 1.2 16 th February, 2009 Introduction The aminoglycosides are a group of naturally occurring or semi-synthetic compounds with bactericidal
More informationPrimary Progressive Multiple Sclerosis
Primary Progressive Multiple Sclerosis A Detailed Overview Pharmascroll A Pharmascroll Publication This publication is meant to be used only for Pharmascroll clients post subscription. Table of Contents
More informationA Brief Introduction to Intersection-Union Tests. Jimmy Akira Doi. North Carolina State University Department of Statistics
Introduction A Brief Introduction to Intersection-Union Tests Often, the quality of a product is determined by several parameters. The product is determined to be acceptable if each of the parameters meets
More informationScientific balance between hazard and risk: the application of TTC in food safety. Richard W. Lane, Ph.D. ILSI NA
Scientific balance between hazard and risk: the application of TTC in food safety Richard W. Lane, Ph.D. ILSI NA Disclaimers I work for PepsiCo I have been associated with ILSI NA for a while Including
More information2.4.QMRF update(s): 3.Defining the endpoint - OECD Principle 1
QMRF identifier (JRC Inventory): QMRF Title: Nonlinear ANN QSAR Model for Repeated dose 90-day oral toxicity study in rodents Printing Date:19.05.2011 1.QSAR identifier 1.1.QSAR identifier (title): Nonlinear
More informationSupporting Information
Supporting Information Discovery of Hydrocarbon-Stapled Short α-helical Peptides as Promising Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Fusion Inhibitors Chao Wang,, Shuai Xia,, Peiyu Zhang,
More informationAntibiotic efflux pumps in eucaryotic cells: consequences for activity against intracellular bacteria
Antibiotic efflux pumps in eucaryotic cells: consequences for activity against intracellular bacteria Unité de Pharmacologie cellulaire et moléculaire F. Van Bambeke Magic bullets need to reach their target
More informationWhat Does It Mean? A Review of Interpreting and Calculating Different Types of Means and Standard Deviations
pharmaceutics Review What Does It Mean? A Review Interpreting Calculating Different Types Means Stard Deviations Marilyn N. Martinez 1, * Mary J. Bartholomew 2 1 Office New Animal Drug Evaluation, Center
More informationIsotope Production for Nuclear Medicine
Isotope Production for Nuclear Medicine Eva Birnbaum Isotope Program Manager February 26 th, 2016 LA-UR-16-21119 Isotopes for Nuclear Medicine More than 20 million nuclear medicine procedures are performed
More informationGroup sequential designs with negative binomial data
Group sequential designs with negative binomial data Ekkehard Glimm 1 Tobias Mütze 2,3 1 Statistical Methodology, Novartis, Basel, Switzerland 2 Department of Medical Statistics, University Medical Center
More informationLecture 21. December 19, Department of Biostatistics Johns Hopkins Bloomberg School of Public Health Johns Hopkins University.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License. Your use of this material constitutes acceptance of that license and the conditions of use of materials on this
More informationElectronic Supplementary Information. Robust Oil-core Nanocapsules with Hyaluronate-based Shells as. Promising NanoVehicles for Lipophilic Compounds
Electronic Supplementary Material (ESI) for Nanoscale. This journal is The Royal Society of Chemistry 2017 Electronic Supplementary Information Robust Oil-core Nanocapsules with Hyaluronate-based Shells
More informationWeighted differential entropy based approaches to dose-escalation in clinical trials
Weighted differential entropy based approaches to dose-escalation in clinical trials Pavel Mozgunov, Thomas Jaki Medical and Pharmaceutical Statistics Research Unit, Department of Mathematics and Statistics,
More informationCleaning Memo for January 2017 A Critique of the APIC Guideline
Cleaning Memo for January 2017 A Critique of the APIC Guideline The APIC Guidance on Aspects of Cleaning Validation in Active Pharmaceutical Ingredient Plants was revised in September 2016. This guide
More informationInfluence of Non Physical Psi Energy of the Soul on Physical Ki Energy of the Body
Influence of Non Physical Psi Energy of the Soul on Physical Ki Energy of the Body Hiroshi Motoyama, Ph.D. President, California Institute for Human Science, California, USA CIHS Journal 2007:Vol. 2 No.
More informationBIOSTATISTICAL METHODS
BIOSTATISTICAL METHODS FOR TRANSLATIONAL & CLINICAL RESEARCH Cross-over Designs #: DESIGNING CLINICAL RESEARCH The subtraction of measurements from the same subject will mostly cancel or minimize effects
More informationUse of Coefficient of Variation in Assessing Variability of Quantitative Assays
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, Nov. 2002, p. 1235 1239 Vol. 9, No. 6 1071-412X/02/$04.00 0 DOI: 10.1128/CDLI.9.6.1235 1239.2002 Use of Coefficient of Variation in Assessing Variability
More informationThe U.S. Food and Drug Administration has approved. Accurate Dose Calibrator Activity Measurement of 90 Y-Ibritumomab Tiuxetan
Accurate Dose Calibrator Activity Measurement of Y-Ibritumomab Tiuxetan Jeffry A. Siegel, PhD 1 ; Brian E. Zimmerman, PhD 2 ; Kory Kodimer, PhD 3 ; Mary A. Dell, MS 4 ; and William E. Simon, MS 5 1 Nuclear
More informationMonte Carlo Simulation
Monte Carlo Simulation Overview Repeatedly draw random samples from a joint parameter probability distribution Calculate outputs given a set of inputs and the simulated parameter values Laboratory of Applied
More information6 Sample Size Calculations
6 Sample Size Calculations A major responsibility of a statistician: sample size calculation. Hypothesis Testing: compare treatment 1 (new treatment) to treatment 2 (standard treatment); Assume continuous
More informationLecture 22: PHARMACY CALCULATIONS for Technicians Preparing Injectable Medications
Lecture 22: PHARMACY CALCULATIONS for Technicians Preparing Injectable Medications PHARMACY CALCULATIONS for Technicians Preparing Injectable Medications This chapter provides an overview of how to determine
More informationPersonalized Treatment Selection Based on Randomized Clinical Trials. Tianxi Cai Department of Biostatistics Harvard School of Public Health
Personalized Treatment Selection Based on Randomized Clinical Trials Tianxi Cai Department of Biostatistics Harvard School of Public Health Outline Motivation A systematic approach to separating subpopulations
More informationArea under Curve Method Development and Validation of Midodrine Hydrocholride
Original Research Article Area under Curve Method Development and Validation of Midodrine Hydrocholride Pritam S. Jain 1,*, Prashant V. Bhadane 2, Harshal P. Chaudhari 3, Sanjay J Surana 4 R.C. Patel Institute
More informationA Comparison of the Bactericidal Activity of Ozone and Chlorine against Escherichia coli at 1 O
381 FETNER, R. H. & INGOLS, R. S. (1956). J. gen. Microbial. 15, 381-385 A Comparison of the Bactericidal Activity of Ozone and Chlorine against Escherichia coli at 1 O BY R. H. FETNER AND R. S. INGOLS
More informationQSAR STUDY OF ANTIMALARIA OF XANTHONE DERIVATIVES USING MULTIPLE LINEAR REGRESSION METHODS
PROCEEDING OF 3 RD INTERNATIONAL CONFERENCE ON RESEARCH, IMPLEMENTATION AND EDUCATION OF MATHEMATICS AND SCIENCE YOGYAKARTA, 16 17 MAY 2016 QSAR STUDY OF ANTIMALARIA OF XANTHONE DERIVATIVES USING MULTIPLE
More informationMembers of WS-3 Working Group
CTTI WS-3 Members of WS-3 Working Group Suzanne Gagnon (Icon Clinical Research) Heather Macy (Pfizer) Rachpal Malhotra (Bristol-Myers Squibb) Margaret McLaughlin (Pfizer) Greg Nadzan (Amgen) Sundeep Sethi
More informationENHANCEMENTS Lash Boost is only to be used as directed by one person. It is not to be shared with other people.
F R E Q U E N T L Y A S K E D Q U E S T I O N S RODAN + FIELDS ENHANCEMENTS LASH BOOST TM W H A T I S E N H A N C E M E N T S L A S H B O O S T? A nightly eyelash conditioning serum that pairs with any
More informationNitroxoline Rationale for the NAK clinical breakpoints, version th October 2013
Nitroxoline Rationale for the NAK clinical breakpoints, version 1.0 4 th October 2013 Foreword NAK The German Antimicrobial Susceptibility Testing Committee (NAK - Nationales Antibiotika-Sensitivitätstest
More informationLOS AMMOS SCIENTIFIC LABORATORY
INKI-AWFIEJI LOS AMMOS SCIENTIFIC LABORATORY OF THE UNIVERSITY OF CALIFORNIA LOS ALAMOS, NEW MEXICO CONTRACTW-7405-ENG36 WITH THE US ATOMIC ENERGY COMMISSION IJNCA5SIHED LOS ALAMOS SCIENTIFIC LABORATORY
More informationCONTINUOUS FLOW CHEMISTRY (PROCESSING) FOR INTERMEDIATES AND APIs
CONTINUOUS FLOW CHEMISTRY (PROCESSING) FOR INTERMEDIATES AND APIs Sripathy Venkatraman, Section Head at AMRI Abstract Many contract manufacturing organizations (CMOs) offer continuous flow chemistry, but
More informationAntibiotic resistance: a real and present danger in our hospitals
Antibiotic resistance: a real and present danger in our hospitals http://www.latimes.com/business/la-fi-hospital-infections-20150218-story.html#page=1 2 The search for new antibacterials HTS based on genetically
More information- 1 - By H. S Steyn, Statistical Consultation Services, North-West University (Potchefstroom Campus)
- 1 - BIOAVAILABILIY AND BIOEQUIVALENCE By H. S Steyn, Statistical Consultation Services, North-West University (Potchefstroom Campus) 1. Bioavailability (see Westlake, 1988) 1.1 Absorption: he aim is
More information