Prediction of Losartan Active Carboxylic Acid Metabolite Exposure Following Losartan Administration Using Static and Physiologically-Based Pharmacokinetic Models.

Prediction of Losartan Active Carboxylic Acid Metabolite Exposure Following Losartan Administration Using Static and Physiologically-Based Pharmacokinetic Models.

Authors: Nguyen HQ, Lin J, Kimoto E, Callegari E, Tse S, Obach RS
Publication: J Pharm Sci
Keywords: allometry, in silico in vitro–in vivo extrapolation (IVIVE), PBPK modeling, transporters
Software: GastroPlus®

The aim of this study was to evaluate a strategy based on static and dynamic physiologically based pharmacokinetic (PBPK) modeling for the prediction of metabolite and parent drug area under...

Development and qualification of physiologically based pharmacokinetic models for drugs with atypical distribution behavior: A desipramine case study.

Development and qualification of physiologically based pharmacokinetic models for drugs with atypical distribution behavior: A desipramine case study.

Authors: Samant TS, Lukacova V, Schmidt S
Publication: CPT Pharmacometrics Syst Pharmacol
Keywords: lysosomal trapping, PBPK modeling, pediatrics, special population
Software: GastroPlus®
Division: PBPK

Desipramine is a secondary tricyclic amine, which is primarily metabolized by cytochrome 2D6. It shows a high volume of distribution (Vss) (10–50 L/kg) due to its high lipophilicity, unspecific phospholipid binding, and lysosomal trapping.

Food effect: The combined effect of media pH and viscosity on the gastrointestinal absorption of ciprofloxacin tablet

Food effect: The combined effect of media pH and viscosity on the gastrointestinal absorption of ciprofloxacin tablet

Authors: Radwan A, Zaid AN, Jaradat N, Odeh Y
Publication: Eur J Pharm Sci
Keywords: ciprofloxacin, corchorus olitorius, food effect, oral absorption, physiological modeling, viscosity
Software: GastroPlus®

The clinical implications of food-drug interactions may have to be taken seriously into account with oral drugs administration in order to minimize variations in drug bioavailability. 

Influence of different proton pump inhibitors on the pharmacokinetics of voriconazole

Influence of different proton pump inhibitors on the pharmacokinetics of voriconazole

Authors: Qi F, Zhu L, Li N, Ge T, Xu G, Liao S
Publication: Int J Antimicrob Agents
Keywords: drug-drug interactions (DDIs), PBPK models, PPI, proton pump inhibitors, voriconazole
Software: GastroPlus®

This study aimed to determine the influence of proton pump inhibitors (PPIs) on the pharmacokinetics of voriconazole and to characterise potential drug-drug interactions (DDIs)...

Systems pharmacology modeling of drug-induced hyperbilirubinemia: Differentiating hepatotoxicity and inhibition of enzymes/transporters

Systems pharmacology modeling of drug-induced hyperbilirubinemia: Differentiating hepatotoxicity and inhibition of enzymes/transporters

Authors: Yang K, Battista C, Woodhead JL, Stahl SH, Mettetal JT, Watkins PB, Siler SQ, Howell BA
Publication: Clin Pharmacol Ther
Keywords: bilirubin, drug exposure, hepatic injury, humans, PBPK, Physiologically based pharmacokinetic (PBPK) modeling, rats
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Elevations in serum bilirubin during drug treatment may indicate global liver dysfunction and a high risk of liver failure.

In vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulation

In vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulation

Authors: O’Shea JP, Murphy C, Ahern RJ, Ryan KB, Griffin BT, Crean AM
Publication: J Control Release
Keywords: dissolution, fenofibrate, hydrodynamics, In vitro–in vivo relationship (IVIVR), mesoporous silica, supersaturation, transfer model
Software: ADMET Predictor®, GastroPlus®

Drug release from mesoporous silica systems has been widely investigated in vitro using USP Type II (paddle) dissolution apparatus.

Lead Antimalarial Identification Using in silico Prediction Methods and Simulation

Lead Antimalarial Identification Using in silico Prediction Methods and Simulation

Authors: Morris D, Woltosz WS, Lawless M, Grasela TH, Clark RD
Conference: ASCPT
Keywords: anti-malarial, FIHSimulator, first-in-human, in silico, malaria, plasma concentration, QSAR, quantitative structure–activity relationships
Software: ADMET Predictor®, GastroPlus®, MedChem Studio™
Division: Clinical Pharmacology and Pharmacometrics (CPP), PBPK

With increasing resistance to currently available antimalarials, new compounds with activity against resistant parasites are needed. Novel compounds were designed and first-in-human (FIH) simulations...

Mechanistic prediction of food effects for Compound A tablet using PBPK model

Mechanistic prediction of food effects for Compound A tablet using PBPK model

Authors: Li X, Shi L, Tang X, Wang Q, Zhou L, Song W, Feng Z, Ge J, Li JK, Yang L, Wen A, Zhang Y
Publication: Saudi J Biol Sci
Keywords: ACAT, Food effects, PBPK, pharmacokinetic, prediction
Software: GastroPlus®
Division: PBPK

Physiologically based pharmacokinetic (PBPK) modeling has been extensively used to study the factors of effect drug absorption, distribution, metabolize and extraction progress in human.

QSP Modeling of Liver AMPK Activation Using NAFLDsym Is Predicted to Reduce Steatosis in NAFLD Patients

QSP Modeling of Liver AMPK Activation Using NAFLDsym Is Predicted to Reduce Steatosis in NAFLD Patients

Authors: Generaux GT, Rieger TR, Howell BA, Allen RJ, Musante CJ, Watkins PB, Siler SQ
Conference: ASCPT
Keywords: liver AMPK activation, Non-alcoholic fatty liver disease (NAFLD), steatosis
Software: NAFLDsym®
Division: Quantitative Systems Pharmacology (QSP)

Non-alcoholic fatty liver disease (NAFLD) currently has few available treatment options. Bringing effective treatments rapidly to market is paramount.

Mechanistic Modeling And Hepatic Biomarker Data From Ggf2 (Cimaglermin Alfa)-Treated Subjects In Phase 1 Clincial Trials Suggest Low Likelihood Of Progressive Liver Injury

Mechanistic Modeling And Hepatic Biomarker Data From Ggf2 (Cimaglermin Alfa)-Treated Subjects In Phase 1 Clincial Trials Suggest Low Likelihood Of Progressive Liver Injury

Authors: Longo DM, Generaux GT, Howell BA, Siler SQ, Antoine DJ, Button D, Caggiano A, Eisen A, Iaci J, Stanulis R, Watkins PB
Conference: ASCPT
Keywords: clinical trials, hepatic biomarker, liver injury, mechanistic modeling
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

GGF2 (USAN cimaglermin alfa) is an investigational drug for the treatment of heart failure. During Phase 1 clinical trials, concomitant, transient elevations in serum aminotransferases (ALT/AST) and...

Use Of Systems Toxicology Modeling To Investigate Mechanisms Of Liver Enzyme Elevations Mediated By Solithromycin And Other Macrolides

Use Of Systems Toxicology Modeling To Investigate Mechanisms Of Liver Enzyme Elevations Mediated By Solithromycin And Other Macrolides

Authors: Yang K, Woodhead JL, Oldach D, MacLauchlin C, Fernandes P, Watkins PB, Siler SQ, Howell BA
Conference: ASCPT
Keywords: liver enzymes, Quantitative Systems Toxicology (QST), solithromycin, systems toxicology modeling
Division: Quantitative Systems Pharmacology (QSP)

Solithromycin, a 4th generation macrolide developed for the treatment of community acquired pneumonia, caused serum liver enzyme (ALT) elevations in clinical studies.