28 Result(s)
within
Neil Parrott
Biomedicine
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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...
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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 (Vd,ss) for small molecule drug candidates is an essential component of assessing likely efficacious dose and clinical safety...
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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...
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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...
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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...
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Article
Correction to: Use of Physiologically Based Pharmacokinetic (PBPK) Modeling for Predicting Drug-Food Interactions: an Industry Perspective
An Erratum to this paper has been published: https://doi.org/10.1208/s12248-020-00535-z
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Article
Correction to: In Vitro to In Vivo Extrapolation of Metabolic Clearance for UGT Substrates Using Short-Term Suspension and Long-Term Co-cultured Human Hepatocytes
During production, the figure captions for Fig. 1 and Fig. 2 were inadvertently switched in the proofing stage.
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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...
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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...
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Article
Open AccessUse of Physiologically Based Pharmacokinetic (PBPK) Modeling for Predicting Drug-Food Interactions: an Industry Perspective
The effect of food on pharmacokinetic properties of drugs is a commonly observed occurrence affecting about 40% of orally administered drugs. Within the pharmaceutical industry, significant resources are inves...
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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...
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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...
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Article
Open AccessImpact of Intracellular Concentrations on Metabolic Drug-Drug Interaction Studies
Accurate prediction of drug-drug interactions (DDI) is a challenging task in drug discovery and development. It requires determination of enzyme inhibition in vitro which is highly system-dependent for many compo...
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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...
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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...
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In Vivo Predictive Dissolution and Simulation Workshop Report: Facilitating the Development of Oral Drug Formulation and the Prediction of Oral Bioperformance
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Article
Investigating Oral Absorption of Carbamazepine in Pediatric Populations
Prediction of the pharmacokinetics of orally administered drugs in children is of importance to optimize the efficacy and safety of pediatric medicines. Physiologically based pharmacokinetic (PBPK) models can ...
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Article
Open AccessProgress in Prediction and Interpretation of Clinically Relevant Metabolic Drug-Drug Interactions: a Minireview Illustrating Recent Developments and Current Opportunities
This review gives a perspective on the current “state of the art” in metabolic drug-drug interaction (DDI) prediction. We highlight areas of successful prediction and illustrate progress in areas where limits ...
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Article
Erratum to: Characterization of Pharmacokinetics in the Göttingen Minipig with Reference Human Drugs: An In Vitro and In Vivo Approach
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Article
Characterization of Pharmacokinetics in the Göttingen Minipig with Reference Human Drugs: An In Vitro and In Vivo Approach
This study aims to expand our understanding of the mechanisms of drug absorption, distribution, metabolism and excretion in the Göttingen minipig to aid a knowledge-driven selection of the optimal species for ...
