Pharmacokinetic/Pharmacodynamic (PK/PD) Model for the Safety of Tigecycline (T) in Patients with Complicated Intra-Abdominal Infections (cIAI)

Pharmacokinetic/Pharmacodynamic (PK/PD) Model for the Safety of Tigecycline (T) in Patients with Complicated Intra-Abdominal Infections (cIAI)

Authors: Meagher AK, Liolios K, Passarell JA, Cirincione B, Van Wart S, Fiedler-Kelly J, Babinchak T, Ellis-Grosse EJ
Conference: ECCMID
Keywords: anti-infectives, antibiotic, antiemetic, cIAI, cSSSI, female, hosmer-lemeshow, infectious disease, Kaplan-Meier, logistic regression, nausea, region, ROC, SAS, vomiting, weight
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Nausea (N) and vomiting (V) have been reported with tigecycline, a new glycylcycline with expanded broad spectrum activity. 140 exposure-response relationships and patient covariates predictive of the first N…

NIPALSTREE:  A New Hierarchical Clustering Approach for Large Compound Libraries and Its Application to Virtual Screening

NIPALSTREE:  A New Hierarchical Clustering Approach for Large Compound Libraries and Its Application to Virtual Screening

Authors: Böcker A, Schneider G, Teckentrup A
Publication: J Chem Inf Model
Keywords: angiotensin converting enzyme (ACE) inhibitors, chemotypes, hierarchical clustering algorithm, MDL Drug Data Report (MDDR)
Software: MedChem Studio™

A hierarchical clustering algorithm NIPALSTREE was developed that is able to analyze large data sets in high-dimensional space. The result can be displayed as a dendrogram.

Pharmacokinetic/pharmacodynamic (PK/PD) Model for Tolvaptan in Healthy Subjects

Pharmacokinetic/pharmacodynamic (PK/PD) Model for Tolvaptan in Healthy Subjects

Authors: Van Wart S, Cirincione B, Ludwig E, Grasela TH, Chen X, Shoaf S, Mallikaarjun S
Conference: ASCPT
Keywords: AIC, Akaike Information Criteria, cardiology, cardiovascular agents, competitive antagonism model, direct effect model, diuretic, Emax, hyponatremia, indirect effect model, NONMEM, output, PE%, UFR, urine flow rate, vasopressin, water intake
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Direct effect, indirect effect, and competitive antagonism models were evaluated to describe plasma tolvaptan concentration effect on urine flow rate (UFR), with consideration of water intake rate (WIR)…

Pharmacokinetic-pharmacodynamic relationships describing the efficacy of oritavancin in patients with Staphylococcus aureus bacteremia

Pharmacokinetic-pharmacodynamic relationships describing the efficacy of oritavancin in patients with Staphylococcus aureus bacteremia

Authors: Bhavnani SM, Passarell JA, Owen JS, Loutit JS, Porter SB, Ambrose PG
Publication: Antimicrob Agents Chemother
Keywords: administration & dosage, analysis, anti-bacterial agents, Bacteremia, Bayes Theorem, classification, comparative study, Dose-Response Relationship, drug, drug therapy, female, Follow-Up Studies, Glycopeptides, humans, infection, logistic models, male
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Bloodstream infections due to antimicrobial-resistant Staphylococcus aureus occur with increasing frequency and represent an important cause of morbidity and mortality.

Are Target-Family-Privileged Substructures Truly Privileged?

Are Target-Family-Privileged Substructures Truly Privileged?

Authors: Schnur DM, Hermsmeier MA, Tebben AJ
Publication: J Med Chem
Keywords: ClassPharmer, G-coupled protein receptor (GCPR), ligands, nuclear hormone receptors, pharmacophores, protein kinases, serine proteases
Software: MedChem Studio™

One of the early and effective approaches to G-coupled protein receptor target family library design was the analysis of a set of ligands for frequently occurring chemical moieties or substructures.

A strategy for preclinical formulation development using GastroPlus™ as pharmacokinetic simulation tool and a statistical screening design applied to a dog study.

A strategy for preclinical formulation development using GastroPlus™ as pharmacokinetic simulation tool and a statistical screening design applied to a dog study.

Authors: Kuentz M, Nick S, Parrott N, Rothlisberger D
Publication: Eur J Pharm Sci
Keywords: bioavailability, clinical formulation, dog studies, factorial design, simulation
Software: GastroPlus®

The aim of this paper is to propose a pharmaceutical risk assessment strategy that goes beyond the usual characterisation of a clinical candidate molecule according to the biopharmaceutical classification system (BCS).

Comparison of censored regression and standard regression analyses for modeling relationships between antimicrobial susceptibility and patient- and institution-specific variables

Comparison of censored regression and standard regression analyses for modeling relationships between antimicrobial susceptibility and patient- and institution-specific variables

Authors: Hammel JP, Bhavnani SM, Jones RN, Forrest A, Ambrose PG
Publication: Antimicrob Agents Chemother
Keywords: anti-bacterial agents, anti-infective agents, Bacterial, biological, comparative study, computer simulation, drug effects, drug resistance, enterobacter, Genetic, humans, linear models, methods, Microbial Sensitivity Tests, models, New York
Division: Clinical Pharmacology and Pharmacometrics (CPP)

In order to identify patients likely to be infected with resistant bacterial pathogens, analytic methods such as standard regression (SR) may be applied to surveillance data to determine patient- and institution-specific...

In Vitro Simulation Adinazolam Mesylate Swellable HPMC Matrix Release Using DDDPlus™ Software

In Vitro Simulation Adinazolam Mesylate Swellable HPMC Matrix Release Using DDDPlus™ Software

Authors: Prabhakaran A, DiBella J, Woltosz WS, Bolger MB
Keywords: adinazolam mesylate, controlled release, dissolution, HPMC, HPMC-Lactose
Software: DDDPlus™
Division: PBPK

Pharmaceutical systems containing a mixture of drug, excipients, and polymer can be used as effective controlled release formulations. The presence of drug and excipients in the polymer matrix creates a…

Population Pharmacokinetics of Tigecycline in Patients with Complicated Skin and Skin-Structure and Intra-Abdominal Infections

Population Pharmacokinetics of Tigecycline in Patients with Complicated Skin and Skin-Structure and Intra-Abdominal Infections

Authors: Van Wart S, Owen JS, Meagher AK, Cirincione B
Conference: ICAAC
Keywords: anti-infectives, antibiotic, bias, cIAI, CrCL, creatinine clearance, cSSSI, dermatology, infectious disease, intravenous, IV, males, NONMEM, PE%, PK, precision, steady state, weight
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Tigecycline is a novel glycylcycline antibiotic with expanded broad-spectrum in vitro activity, including emerging multidrug-resistant pathogens. The goal of this analysis was to develop a PPK model for…

Noncompartmental Pharmacokinetics of Tigecycline in Phase 3 Studies of Patients with Complicated Skin and Skin-Structure and Intra-Abdominal Infections

Noncompartmental Pharmacokinetics of Tigecycline in Phase 3 Studies of Patients with Complicated Skin and Skin-Structure and Intra-Abdominal Infections

Authors: Darling IM, Cirincione B, Owen JS
Conference: ICAAC
Keywords: anti-infectives, antibiotic, cIAI, cSSSI, dermatology, infectious disease, intravenous, IV, noncompartmental, steady state, WinNonlin
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Tigecycline is the first glycylcycline to reach Phase 3 clinical trials and is active against multidrug-resistant organisms. Four Phase 3 studies have examined tigecycline for the treatment of complicated…