Physiologically-Based Model for Fluvoxamine Disposition and Prediction of Drug-Drug Interactions

Physiologically-Based Model for Fluvoxamine Disposition and Prediction of Drug-Drug Interactions

Authors: Chung J, Lukacova V, Parrott N, Woltosz WS, Bolger MB
Conference: DDI
Keywords: absorption, ACAT model, DDIs, drug-drug interactions (DDIs), fluvoxamine, PBPK, tissue:plasma
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

Fluvoxamine absorption and pharmacokinetics were simulated using GastroPlus™. The program’s Advanced Compartmental and Transit model described the absorption; pharmacokinetics was simulated with a…

Prediction of drug -drug interactions for fluconazole using PBPK – a case with concentration-dependent liver:plasma partition coefficient

Prediction of drug -drug interactions for fluconazole using PBPK – a case with concentration-dependent liver:plasma partition coefficient

Authors: Fraczkiewicz G, Parrott N, Lukacova V, Bolger MB, Crison JR, Woltosz WS, Lavé T
Conference: DDI
Keywords: ADMET, antifungal, candidiasis, DDI predictions, DDIs, drug-drug interactions (DDIs), fluconazole, liver:plasma, meningitis, PBPK
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

Fluconazole is an antifungal agent widely used in the clinical setting for the treatment of candidiasis and meningitis. It undergoes minimal metabolism and is excreted renally(1). Fluconazole is a moderate…

Timing and incidence of postoperative infections associated with blood transfusions: analysis of 1,489 orthopedic and cardiac surgery patients

Timing and incidence of postoperative infections associated with blood transfusions: analysis of 1,489 orthopedic and cardiac surgery patients

Authors: Shander A, Spence RK, Shore-Lesserson L, Walawander CA
Publication: Surg Infect
Keywords: allogeneic blood transfusion, cardiology, cardiovascular, orthopedics
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Transfusion rates remain high in cardiac and orthopedic surgery and differ widely across physician practices in spite of growing knowledge that allogeneic...

Modeling Drug Disposition in Ocular Tissues following Topical Eye Drops and Intravitreal Injection

Modeling Drug Disposition in Ocular Tissues following Topical Eye Drops and Intravitreal Injection

Authors: Chaudhuri S, Crison JR, Lukacova V, Bolger MB, Woltosz WS
Conference: ARVO
Keywords: absorption, ADMET, clearance, clonidine, cornea, Distribution, eye, glaucoma, ocular, ocular metabolism
Software: GastroPlus®
Division: PBPK

The purpose of this study was to model the ocular absorption, distribution and clearance of clonidine and voriconazole from topical and intravitreal applications, respectively. Clonidine is a potent…

Computer simulations using GastroPlus to justify a biowaiver for etoricoxib solid oral drug products

Computer simulations using GastroPlus to justify a biowaiver for etoricoxib solid oral drug products

Authors: Okumu A, DiMaso M, Loebenberg R
Publication: Eur J Pharm Biopharm
Keywords: Caco-2 cells, computer simulation, dosage, drug delivery, humans, hydrogen-ion concentration, permeability, pharmaceutical chemistry, pharmaceutical preparations, Pyridines, solubility, Sulfones, therapeutic equivalency, x-ray diffraction
Software: GastroPlus®

The purpose of this study was to compare the dissolution behaviour of etoricoxib in different dissolution media and to establish in vitro/in vivo correlation (IVIVC) using computer simulations.

Non-competitive androgen receptor inhibition in vitro and in vivo

Non-competitive androgen receptor inhibition in vitro and in vivo

Authors: Jones JO, Bolton EC, Huang Y, Feau C, Guy RK, Yamamoto KR, Hann B, Diamond MI
Publication: Proc Natl Acad Sci USA
Keywords: Androgen receptor (AR), AR-dependent gene expression, benign prostatic hypertrophy, hirsutism, Pyrvinium
Division: PBPK

Androgen receptor (AR) inhibitors are used to treat multiple human diseases, including hirsutism, benign prostatic hypertrophy, and prostate cancer, but all available...

Kerfuffle!

Kerfuffle!

Authors: Grasela TH, Ludwig EA, Fiedler-Kelly J
Publication: J Clin Pharmacol
Keywords: Clinical Trials as Topic, Cost-Benefit Analysis, drug design, drug discovery, forensic pharmacometrics, humans, methods, research design
Division: Clinical Pharmacology and Pharmacometrics (CPP)

To become disheveled. A kerfuffle is the polite term for a cascading series of errors that can be initiated by a seemingly innocuous event that then leads to other...

Development of a Steady-State Exposure-Response Model for Exenatide Once Weekly

Development of a Steady-State Exposure-Response Model for Exenatide Once Weekly

Authors: Cirincione B, Passarell JA, Kothare PA, Cummings M, Grasela TH, Fineman MS
Conference: ASCPT
Keywords: antidiabetic agents, body mass index, CrCL, Endocrinology, exendin, glycated hemoglobin, hemoglobin A1c, hormones, ideal body weight, metformin, pharmacodynamic, pharmacokinetic, PK/PD, QW, renal function, subcutaneous, sulfonylurea, thiazolidinedione
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Exenatide is dosed as a subcutaneous (SC) injection of 5 and 10 μg twice daily (BID) before main meals and is indicated for the treatment of type 2 diabetes mellitus in patients failing to achieve adequate…

Predicting pharmacokinetics of drugs using physiologically based modeling – application to food effects

Predicting pharmacokinetics of drugs using physiologically based modeling – application to food effects

Authors: Parrott N, Lukacova V, Fraczkiewicz G, Bolger MB
Publication: AAPS J
Keywords: adenocarinoma pathology, animals, biological models, cell line, chemical precipitation, colonic neoplasms, computer simulation, dogs, eating, fasting, food-drug interactions, gastrointestinal tract (GIT), hydrogen-ion concentration, intestinal absorption, pharmaceutical chemistry, pharmacokinetics, solubility, Theophylline, tumor metabolism
Software: GastroPlus®
Division: PBPK

Our knowledge of the major mechanisms underlying the effect of food on drug absorption allows reliable qualitative prediction based on biopharmaceutical properties...

Calculation of molecular lipophilicity: State-of-the-art and comparison of log P methods on more than 96,000 compounds

Calculation of molecular lipophilicity: State-of-the-art and comparison of log P methods on more than 96,000 compounds

Authors: Mannhold R, Poda GI, Ostermann C, Tetko IV
Publication: J Pharm Sci
Keywords: drug design, humans, lipids chemistry, mathematical computing, molecular models
Software: ADMET Predictor®

We first review the state-of-the-art in development of log P prediction approaches falling in two major categories: substructure-based and property-based methods.

Application of patient population-derived pharmacokinetic-pharmacodynamic relationships to tigecycline breakpoint determination for staphylococci and streptococci

Application of patient population-derived pharmacokinetic-pharmacodynamic relationships to tigecycline breakpoint determination for staphylococci and streptococci

Keywords: AUC, exposure-response, MIC, Monte Carlo, PK, simulations, Staphylococcus aureus, streptococci
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Correctly determined susceptibility breakpoints are important to both the individual patient and to society at large. A previously derived patient population...

Toward an In Vivo Dissolution Methodology: A Comparison of Phosphate and Bicarbonate Buffers

Toward an In Vivo Dissolution Methodology: A Comparison of Phosphate and Bicarbonate Buffers

Authors: Sheng JJ, McNamara DP, Amidon GL
Publication: Mol Pharm
Keywords: bicarbonates chemistry, biological models, buffers, hydrogen-ion concentration, pharmaceutical chemistry, pharmaceutical preparations, phosphates chemistry, pKa, solubility
Software: ADMET Predictor®

The purpose of this research was to evaluate the difference between the pharmaceutical phosphate buffers and the gastrointestinal bicarbonates in dissolution of ketoprofen and indomethacin...