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…

Adult and Pediatric GastroPlus-PBPK Simulations of Gabapentin using in silico Population Estimates for Age-Related (PEAR) Physiology

Adult and Pediatric GastroPlus-PBPK Simulations of Gabapentin using in silico Population Estimates for Age-Related (PEAR) Physiology

Authors: Bolger MB, Chittenden J, Woltosz WS
Conference: AAPS
Keywords: midazolam, PEAR, Population Estimates for Age-Related (PEAR™) Physiology™
Software: GastroPlus®
Division: PBPK

To evaluate the accuracy of prediction of Midazolam absorption and bioavailability in a pediatric population from in silico, in vitro and adult in vivo data. The significance of scaling of the clearance and…

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

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

Authors: Van Wart S, Owen JS, Meagher AK, Cirincione B
Conference: AAPS
Keywords: anti-infectives, antibiotic, bias, cIAI, cSSSI, dermatology, infectious disease, intravenous, IV, NONMEM, PE%, PK, precision, sparse sampling
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Tigecycline is a novel glycylcycline antibiotic demonstrating broad-spectrum in vitro activity. A previously developed population pharmacokinetic (PK) model was utilized to generate individual predicted…

Population Pharmacokinetics of Modafinil Film-Coated Tablets in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Population Pharmacokinetics of Modafinil Film-Coated Tablets in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Authors: Owen JS, Grasela TH, Robertson P, Darwish M
Conference: AAPS
Keywords: ADHD, age, central nervous system agents, full-profile, induction, neurology, NONMEM, PE%, pediatrics, PK, sparse sampling, validation, weight
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Modafinil is currently being evaluated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. A population pharmacokinetic model was developed…

Pharmacokinetic/Pharmacodynamic Model for the Safety of Tigecycline in Patients with Complicated Skin and Skin-Structure Infections

Pharmacokinetic/Pharmacodynamic Model for the Safety of Tigecycline in Patients with Complicated Skin and Skin-Structure Infections

Authors: Meagher AK, Passarell JA, Liolios K, Cirincione B, Van Wart S, Grasela TH, Babinchak T, Ellis-Grosse EJ
Conference: IDSA
Keywords: age, anti-infectives, antibiotic, cSSSI, dermatology, dose, hosmer-lemeshow, infectious disease, intravenous, IV, Kaplan-Meier, logistic regression, males, nausea, PK/PD, region, ROC, SAS, vomiting
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Tigecycline is a first-in-class glycylcycline for the treatment of serious bacterial infections. Reported adverse events from clinical trials include nausea and vomiting. Exposure-response relationships and…

Challenges in the transition to model-based development

Challenges in the transition to model-based development

Authors: Grasela TH, Fiedler-Kelly J, Walawander CA, Owen JS, Cirincione BB, Reitz KE, Ludwig EA, Passarell JA, Dement CW
Publication: AAPS J
Keywords: animals, decision-making, guidelines, humans, methods, Models: Theoretical, pharmacokinetics, Technology: Pharmaceutical
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Practitioners of the art and science of pharmacometrics are well aware of the considerable effort required to successfully complete modeling and simulation activities...

An evaluation of the utility of physiologically based models of pharmacokinetics in early drug discovery

An evaluation of the utility of physiologically based models of pharmacokinetics in early drug discovery

Authors: Parrott N, Paquereau N, Coassolo P, Lavé T
Publication: J Pharm Sci
Keywords: animals, area under curve, biological availability, biological models, blood, chemistry, computer simulation, drug design, intestinal absorption, metabolism, pharmaceutical preparations, pharmacokinetic, rats, solubility
Software: GastroPlus®

Generic physiologically-based models of pharmacokinetics were evaluated for early drug discovery.