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: Simulations Plus

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: Cognigen

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: Cognigen

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: Cognigen

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: Cognigen

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.

Use of pharmacokinetic-pharmacodynamic target attainment analyses to support phase 2 and 3 dosing strategies for doripenem

Use of pharmacokinetic-pharmacodynamic target attainment analyses to support phase 2 and 3 dosing strategies for doripenem

Authors: Bhavnani SM, Hammel JP, Cirincione B, Wikler MA, Ambrose PG
Publication: Antimicrob Agents Chemother
Keywords: administration & dosage, adolescent, adult, aged, bacteria, bacterial infections, biological, Carbapenems, doripenem population, double-blind method, drug effects, female, humans, infusions, intravenous, male, Microbial Sensitivity Tests, microbiology, middle-aged, models
Division: Cognigen

A doripenem population pharmacokinetic model and Monte Carlo simulations were utilized for dose regimen decision support for future clinical development.

Pharmacokinetic/pharmacodynamic profile for tigecycline-a new glycylcycline antimicrobial agent

Pharmacokinetic/pharmacodynamic profile for tigecycline-a new glycylcycline antimicrobial agent

Authors: Meagher AK, Ambrose PG, Grasela TH, Ellis-Grosse EJ
Publication: Diagn Microbiol Infect Dis
Keywords: administration & dosage, Age Factors, analogs & derivatives, animals, anti-bacterial agents, antibio, bacteria, bacterial infections, blister, glycylcycline, half-life, humans, infusions, intravenous, metabolism, Microbial Sensitivity Tests, Minocycline, pharmacokinetics, Tigecycline
Division: Cognigen
Antimicrobial safety: focus on fluoroquinolones

Antimicrobial safety: focus on fluoroquinolones

Authors: Owens RC, Ambrose PG
Publication: Clin Infect Dis
Keywords: 80 and over, adult, adverse effects, aged, Anaphylaxis, animals, Arrhythmias, cardiac, chemically induced, chemistry, child, clinical trials, Dermatitis, Enterocolitis, fluoroquinolones, glucose, headache, homeostasis, humans, Phototoxic, Pseudomembranous
Division: Cognigen

Infrequent toxicities associated with certain drugs and drug classes have recently gained much attention from different health-care perspectives.

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: Cognigen

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: Cognigen

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