Development Of A Pharmacokinetic (Pk) Model And Assessment Of Patient (Pt) Covariate Effects On Dose-Dependent Pk Following Different Dosing Schedules In Two Phase I Trials Of Ap23573 (Ap), An Mtor Inhibitor

Development Of A Pharmacokinetic (Pk) Model And Assessment Of Patient (Pt) Covariate Effects On Dose-Dependent Pk Following Different Dosing Schedules In Two Phase I Trials Of Ap23573 (Ap), An Mtor Inhibitor

Authors: Desai AA, Mita M, Fetterly GJ, Chang C, Netsch M, Knowles HL, Bedrosian CL, Rowinsky E, Tolcher A, Ratain MJ
Conference: ASCO
Keywords: antineoplastics, body surface area, BSA, cancer, dose, dose-limiting toxicity, maximum tolerated dose, MTD, mucositis, Oncology, RBC, red blood cell, safety, WinNonlin
Division: Clinical Pharmacology and Pharmacometrics (CPP)

AP23573 is a novel non-prodrug rapamycin analog that potently inhibits mTOR (through bivalent binding to FKBP and mTOR), a downstream effector of PI3K/Akt and nutrient-sensing pathways. A PK model was…

Application of an in vitro infection model and simulation for reevaluation of fluoroquinolone breakpoints for Salmonella enterica serotype typhi

Application of an in vitro infection model and simulation for reevaluation of fluoroquinolone breakpoints for Salmonella enterica serotype typhi

Authors: Booker BM, Smith PF, Forrest A, Bullock J, Kelchlin P, Bhavnani SM, Jones RN, Ambrose PG
Publication: Antimicrob Agents Chemother
Keywords: administration & dosage, anti-infective agents, area under curve, ciprofloxacin, computer simulation, Dose-Response Relationship, drug, drug effects, drug therapy, fluoroquinolone therapy, fluoroquinolones, half-life, in vitro, infection, Microbial Sensitivity Tests, microbiology
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Salmonella enterica serotype Typhi and nontyphoidal Salmonella remain major causes of morbidity and mortality worldwide.

Pharmacodynamic Characterization of NVP-LMB415 against Haemophilus Influenzae in an In Vitro Hollow-Fiber System

Pharmacodynamic Characterization of NVP-LMB415 against Haemophilus Influenzae in an In Vitro Hollow-Fiber System

Authors: Meagher AK, Smith P, Forrest A, Ogundele A, Ambrose PG
Conference: ECCMID
Keywords: anti-infectives, antibiotic, AUC:MIC ratio, CFU, continuous infusion, exposure-response, H flu, H influenzae, infectious disease, PK/PD, resistance
Division: Clinical Pharmacology and Pharmacometrics (CPP)

NVP-LBM415 is a peptide deformylase inhibitor with in vitro activity against those pathogens commonly associated with community-acquired respiratory tract infections. The purpose of these studies was to…

Exposure-Response Analysis Of The Efficacy Of Tigecycline In Patients With Complicated Skin And Skin-Structure Infections

Exposure-Response Analysis Of The Efficacy Of Tigecycline In Patients With Complicated Skin And Skin-Structure Infections

Authors: Meagher AK, Passarell JA, Cirincione B, Van Wart S, Liolios K, Babinchak T, Ellis-Grosse EJ, Ambrose PG
Conference: ECCMID
Keywords: anti-infectives, antibiotic, AUC:MIC ratio, CART, classification and regression tree, cSSSI, dermatology, exposure-response, GEE, infectious disease, IV, logistic regression, pharmacodynamic, PK/PD, S-Plus, s.aureus, SAS, staphylococcus, steady state, streptococcus
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Tigecycline, the first glycylcycline to reach clinical trials, is in development for the treatment of patients with serious infections, including complicated skin and skin-structure infections (cSSSI).

Pharmacokinetic/Pharmacodynamic Model For The Tolerability Of Tigecycline In Healthy Volunteers

Pharmacokinetic/Pharmacodynamic Model For The Tolerability Of Tigecycline In Healthy Volunteers

Authors: Passarell JA, Meagher AK, Liolios K, Grasela TH, Babinchak T, Ellis-Grosse EJ
Conference: ECCMID
Keywords: anti-infectives, antibiotic, exposure-response, infectious disease, intravenous, IV, Kaplan-Meier, logistic regression, nausea, safety, vomiting
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Tigecycline, a first-in-class glycylcycline, is an antimicrobial agent with demonstrated in vitro activity against susceptible and multiple-drug resistant gram-positive and gram-negative bacteria.

A Novel Approach For Evaluating The Microbiological Efficacy Of Tigecycline In Patients With Complicated Skin And Skin-Structure Infections

A Novel Approach For Evaluating The Microbiological Efficacy Of Tigecycline In Patients With Complicated Skin And Skin-Structure Infections

Authors: Meagher AK, Ambrose PG, Passarell JA, Cirincione B, Babinchak T, Ellis-Grosse EJ
Conference: ECCMID
Keywords: anti-infectives, antibiotic, AUC:MIC ratio, cSSSI, dermatology, exposure-response, GEE, gram-positive, hosmer-lemeshow, infectious disease, intravenous, IV, logistic regression, ROC, s.aureus, steady state, streptococcus
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Tigecycline is a glycylcycline in development for the treatment of patients with serious infections, including complicated skin and skin-structure infections (cSSSI). While cSSSI can be caused by a…

Classifying “Kinase Inhibitor‐Likeness” by Using Machine‐Learning Methods

Classifying “Kinase Inhibitor‐Likeness” by Using Machine‐Learning Methods

Authors: Briem H, Gunther J
Publication: Chembiochem
Keywords: artificial neural networks (ANN), k nearest neighbor classification with GA-optimized feature selection (GA/kNN), kinase inhibitors, recursive partitioning (RP), support-vector machines (SVM)
Software: MedChem Studio™

By using an in-house data set of small-molecule structures, encoded by Ghose–Crippen parameters, several machine learning techniques were applied to distinguish between kinase inhibitors...

Application of Full Physiological Models for Pharmaceutical Drug Candidate Selection and Extrapolation of Pharmacokinetics to Man

Application of Full Physiological Models for Pharmaceutical Drug Candidate Selection and Extrapolation of Pharmacokinetics to Man

Authors: Parrott N, Jones HM, Paquereau N, Lavé T
Publication: Basic Clin Pharmacol Toxicol
Keywords: dose selection, in vivo, pharmacokinetics, simulation
Software: GastroPlus®

This paper describes how we are applying physiologically based models of pharmacokinetics as an integrated part in the research and preclinical development of novel drugs.

Relationship between increased levofloxacin use and decreased susceptibility of Streptococcus pneumoniae in the United States

Relationship between increased levofloxacin use and decreased susceptibility of Streptococcus pneumoniae in the United States

Authors: Bhavnani SM, Hammel JP, Jones RN, Ambrose PG
Publication: Diagn Microbiol Infect Dis
Keywords: anti-bacterial agents, Bacterial, Community-Acquired Infections, diagnosis, drug effects, drug resistance, drug therapy, fluoroquinolones, humans, Microbial Sensitivity Tests, ofloxacin, pharmacology, Pneumococcal Infections, statistics
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Increasing reports of fluoroquinolone-non-susceptible Streptococcus pneumoniae are of clinical concern. We examined the relationship between outpatient fluoroquinolone...

Pharmacokinetics of oritavancin in plasma and skin blister fluid following administration of a 200-milligram dose for 3 days or a single 800-milligram dose

Pharmacokinetics of oritavancin in plasma and skin blister fluid following administration of a 200-milligram dose for 3 days or a single 800-milligram dose

Authors: Fetterly GJ, Ong CM, Bhavnani SM, Loutit JS, Porter SB, Morello LG, Ambrose PG, Nicolau DP
Publication: Antimicrob Agents Chemother
Keywords: administration & dosage, adult, analysis, anti-bacterial agents, area under curve, blister, cSSSI, Dose-Response Relationship, drug, drug therapy, Glycopeptides, humans, infection, male, Mass Spectrometry, metabolism, middle-aged, oritavancin, pharmacokinetics, plasma
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Oritavancin is a novel glycopeptide currently being developed for the treatment of complicated skin and skin structure infections (cSSSI), including those caused by multidrug...

Assessment of pharmacokinetic-pharmacodynamic target attainment of gemifloxacin against Streptococcus pneumoniae

Assessment of pharmacokinetic-pharmacodynamic target attainment of gemifloxacin against Streptococcus pneumoniae

Authors: Owens RC, Bhavnani SM, Ambrose PG
Publication: Diagn Microbiol Infect Dis
Keywords: anti-bacterial agents, Bacterial, ciprofloxacin, drug effects, drug resistance, fluoroquinolones, humans, infection, Monte Carlo Method, Naphthyridines, ofloxacin, pharmacokinetics, pharmacology, Probability, research, Respiratory Tract Infections
Division: Clinical Pharmacology and Pharmacometrics (CPP)

The treatment of community-acquired respiratory tract infections has been complicated by the emergence of multidrug-resistant Streptococcus pneumoniae.

Population pharmacokinetics and pharmacodynamics of garenoxacin in patients with community-acquired respiratory tract infections

Population pharmacokinetics and pharmacodynamics of garenoxacin in patients with community-acquired respiratory tract infections

Authors: Van Wart S, Phillips L, Ludwig E, Russo R, Gajjar DA
Publication: Antimicrob Agents Chemother
Keywords: 80 and over, adolescent, adult, adverse effects, aged, analysis, anti-bacterial agents, area under curve, body weight, Bronchitis, classification, clinical trials, Community-Acquired Infections, Creatinine, drug interactions, drug therapy, female
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Garenoxacin (T-3811ME, BMS-284756) is a novel, broad-spectrum des-F(6) quinolone currently under study for the treatment of community-acquired respiratory tract infections.

Effect of Hepatic Impairment on the Pharmacokinetics of the Novel Glycopeptide Oritavancin

Effect of Hepatic Impairment on the Pharmacokinetics of the Novel Glycopeptide Oritavancin

Authors: Fetterly GJ, Owen JS, Bhavnani SM, Ambrose PG, Morello L, Loutit JS, Porter SB
Conference: AAPS
Keywords: adult, anti-infectives, antibiotic, Child-Pugh, gram-positive, infectious disease, intravenous, IV, liver, MRSA, non compartmental, oritavancin, PK
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Oritavancin (ORI) is a semisynthetic glycopeptide being developed for the treatment of serious gram-positive infections. Physiochemical properties of ORI lead to extensive tissue distribution, with uptake…

Evaluation of the Bias and Precision of Bayesian Parameter Estimates When Applying a Phase I Model to Sparse Patient Data

Evaluation of the Bias and Precision of Bayesian Parameter Estimates When Applying a Phase I Model to Sparse Patient Data

Authors: Van Wart S, Phillips L, Grasela TH
Conference: AAPS
Keywords: full-profile, IIV, interindividual variability, NONMEM, PE%, PK, PKPD methodology, residual variability, RV, SAS, simulation, sparse sampling
Division: Clinical Pharmacology and Pharmacometrics (CPP)

A simulation study was conducted to assess the use of a Phase 1 population PK model to estimate Bayesian parameters in Phase 2/3 patients. Specifically, the bias and precision of the Bayesian parameter…

Monte Carlo Simulation To Estimate In Vitro Susceptibility Breakpoints For Moxifloxacin, Gatifloxacin, And Levofloxacin Against Staphylococcus Aureus

Monte Carlo Simulation To Estimate In Vitro Susceptibility Breakpoints For Moxifloxacin, Gatifloxacin, And Levofloxacin Against Staphylococcus Aureus

Authors: Meagher AK, Craig WA, Jones RN, Dalhoff A, Stass H, Ambrose PG
Conference: ICAAC
Keywords: anti-infectives, AUC:MIC ratio, CFU, gram-positive, infectious disease, MIC, mice, murine, non compartmental, noncompartmental, nonlinear, oral, PK/PD, quinolone, resistance, T>MIC
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Emerging resistance with staphylococci has called for a change in treatment paradigms and review of breakpoints. Current NCCLS breakpoints for gatifloxacin and levofloxacin against Staphylococcus spp...