38 Result(s)

Article

Streamlining Food Effect Assessment — Are Repeated Food Effect Studies Needed? An IQ Analysis

Current regulatory guidelines on drug-food interactions recommend an early assessment of food effect to inform clinical dosing instructions, as well as a pivotal food effect study on the to-be-marketed formula...

Filippos Kesisoglou, Sumit Basu, Tejashree Belubbi, Philip Bransford… in The AAPS Journal (2023)

Article

Current Approaches for Predicting Human PK for Small Molecule Development Candidates: Findings from the IQ Human PK Prediction Working Group Survey

Accurate prediction of human clearance (CL) and volume of distribution at steady state (V_d,ss) for small molecule drug candidates is an essential component of assessing likely efficacious dose and clinical safety...

Carl Petersson, **n Zhou, Joerg Berghausen, David Cebrian… in The AAPS Journal (2022)

Article

Physiologically-Based Pharmacokinetic Modelling of Entrectinib Parent and Active Metabolite to Support Regulatory Decision-Making

Entrectinib is a selective inhibitor of ROS1/TRK/ALK kinases, recently approved for oncology indications. Entrectinib is predominantly cleared by cytochrome P450 (CYP) 3A4, and modulation of CYP3A enzyme activ...

Nassim Djebli, Vincent Buchheit… in European Journal of Drug Metabolism and Ph… (2021)

Article

Use of Physiologically Based Pharmacokinetic Modeling for Predicting Drug–Food Interactions: Recommendations for Improving Predictive Performance of Low Confidence Food Effect Models

Food can alter drug absorption and impact safety and efficacy. Besides conducting clinical studies, in vitro approaches such as biorelevant solubility and dissolution testing and in vivo dog studies are typical a...

Christian Wagner, Filippos Kesisoglou, Xavier J. H. Pepin, Neil Parrott… in The AAPS Journal (2021)

Article

Understanding Mechanisms of Food Effect and Develo** Reliable PBPK Models Using a Middle-out Approach

Over the last 10 years, 40% of approved oral drugs exhibited a significant effect of food on their pharmacokinetics (PK) and currently the only method to characterize the effect of food on drug absorption, whi...

Xavier J. H. Pepin, James E. Huckle, Ravindra V. Alluri, Sumit Basu… in The AAPS Journal (2021)

Article

In Vitro to In Vivo Extrapolation of Metabolic Clearance for UGT Substrates Using Short-Term Suspension and Long-Term Co-cultured Human Hepatocytes

The use of micro-patterned co-cultured hepatocytes for human hepatic clearance predictions has previously been demonstrated using drugs metabolized by cytochrome P450 enzymes. The present study evaluates the in v...

Luca Docci, Florian Klammers, Aynur Ekiciler, Birgit Molitor… in The AAPS Journal (2020)

Article

Construction and Verification of Physiologically Based Pharmacokinetic Models for Four Drugs Majorly Cleared by Glucuronidation: Lorazepam, Oxazepam, Naloxone, and Zidovudine

Physiologically based pharmacokinetic (PBPK) modeling is less well established for substrates of UDP-glucuronosyltransferases (UGT) than for cytochrome P450 (CYP) metabolized drugs and more verification of sim...

Luca Docci, Kenichi Umehara, Stephan Krähenbühl, Stephen Fowler… in The AAPS Journal (2020)

Article

Physiologically Based Absorption Modelling to Explore the Impact of Food and Gastric pH Changes on the Pharmacokinetics of Entrectinib

Entrectinib is a potent and selective tyrosine kinase inhibitor (TKI) of TRKA/B/C, ROS1, and ALK with both systemic and CNS activities, which has recently received FDA approval for ROS1 fusion-positive non-sma...

Neil Parrott, Cordula Stillhart, Marc Lindenberg, Bjoern Wagner… in The AAPS Journal (2020)

Article

Global Sensitivity Analysis of the Rodgers and Rowland Model for Prediction of Tissue: Plasma Partitioning Coefficients: Assessment of the Key Physiological and Physicochemical Factors That Determine Small-Molecule Tissue Distribution

In physiologically based pharmacokinetic (PBPK) modelling, the large number of input parameters, limited amount of available data and the structural model complexity generally hinder simultaneous estimation of...

Estelle Yau, Andrés Olivares-Morales, Michael Gertz, Neil Parrott… in The AAPS Journal (2020)

Article

Simulating the Impact of Elevated Levels of Interleukin-6 on the Pharmacokinetics of Various CYP450 Substrates in Patients with Neuromyelitis Optica or Neuromyelitis Optica Spectrum Disorders in Different Ethnic Populations

A physiologically based pharmacokinetic (PBPK) model was used to simulate the impact of elevated levels of interleukin (IL)-6 on the exposure of several orally administered cytochrome P450 (CYP) probe substrat...

Krishna K. Machavaram, Chihiro Endo-Tsukude, Kimio Terao… in The AAPS Journal (2019)

Article

The Ontogeny of UDP-glucuronosyltransferase Enzymes, Recommendations for Future Profiling Studies and Application Through Physiologically Based Pharmacokinetic Modelling

Limited understanding of drug pharmacokinetics in children is one of the major challenges in paediatric drug development. This is most critical in neonates and infants owing to rapid changes in physiological f...

Justine Badée, Stephen Fowler, Saskia N. de Wildt… in Clinical Pharmacokinetics (2019)

Article

PBPK Absorption Modeling: Establishing the In Vitro–In Vivo Link—Industry Perspective

The establishment of an in vitro–in vivo correlation (IVIVC) is considered the gold standard to establish in vivo relevance of a dissolution method and to utilize dissolution data in the context of regulatory bio...

Cordula Stillhart, Xavier Pepin, Christophe Tistaert, David Good… in The AAPS Journal (2019)

Article

In Vivo Predictive Dissolution and Simulation Workshop Report: Facilitating the Development of Oral Drug Formulation and the Prediction of Oral Bioperformance

Yasuhiro Tsume, Sanjaykumar Patel, Nikoletta Fotaki, Christel Bergstrӧm… in The AAPS Journal (2018)