Physiologically Based Pharmacokinetic Modeling of Impaired Carboxylesterase-1 Activity: Effects on Oseltamivir Disposition

@article{Hu2014PhysiologicallyBP,
  title={Physiologically Based Pharmacokinetic Modeling of Impaired Carboxylesterase-1 Activity: Effects on Oseltamivir Disposition},
  author={Zhe-yi Hu and A. Edginton and S. Laizure and R. B. Parker},
  journal={Clinical Pharmacokinetics},
  year={2014},
  volume={53},
  pages={825-836}
}
Background and ObjectiveHuman carboxylesterase-1 (CES1) is an enzyme that is primarily expressed in the liver, where it plays an important role in the metabolism of many commonly used medications. Ethanol (alcohol)-mediated inhibition of CES1 and loss-of-function polymorphisms in the CES1 gene can markedly reduce this enzyme’s function. Such alterations in CES1 activity may have important effects on the disposition of substrate drugs. The aim of this study is to develop a physiologically based… Expand
Carboxylesterase 1 and Precision Pharmacotherapy: Pharmacogenetics and Nongenetic Regulators
TLDR
Predicting the hepatic CES1 function can provide clinical guidance to optimize pharmacotherapy of numerous medications metabolized by CES1, and genetic polymorphisms, including single-nucleotide polymorphisms and copy number variants and nongenetic contributors, that could influence CES1 functionality and the PK and PD of CES1 substrates are discussed. Expand
Age-Dependent Absolute Abundance of Hepatic Carboxylesterases (CES1 and CES2) by LC-MS/MS Proteomics: Application to PBPK Modeling of Oseltamivir In Vivo Pharmacokinetics in Infants
TLDR
The age-dependent absolute protein abundance of carboxylesterase 1 and CES2 in human liver was investigated and applied to predict infant pharmacokinetics (PK) of oseltamivir in infants using pediatric physiologically based PK modeling and incorporating the protein abundance–based ontogeny function into the existing pediatric Simcyp model. Expand
Challenges and Opportunities with Non-CYP Enzymes Aldehyde Oxidase, Carboxylesterase, and UDP-Glucuronosyltransferase: Focus on Reaction Phenotyping and Prediction of Human Clearance
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Progress made in establishing in vitro-in vivo correlation, predicting human clearance and avoiding costly clinical failures when non-CYP-mediated metabolic pathways are predominant are highlighted. Expand
Using a Physiologically Based Pharmacokinetic Absorption Model to Establish Dissolution Bioequivalence Safe Space for Oseltamivir in Adult and Pediatric Populations
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Results indicate that the generic products with 10% slower dissolution profile than the pivotal reference bio-batch could still maintain BE to the reference in adults, and a stringent trend of dissolution boundary is observed for pediatrics to maintain BE. Expand
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A lack of consistency in model development and quality assessment practices is revealed, demonstrating a need for development of best-practice guidelines. Expand
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Current state of knowledge on the usefulness of PBPK modeling in estimation of drug exposure in specific medical conditions including pregnancy, pediatrics, elderly, patients with liver or renal impairment, obesity, and following bariatric surgery were outlined. Expand
Physiologically Based Pharmacokinetic ( PBPK ) Modeling and Simulation Approaches : A Systematic Review of Published Models , Applications , and Model Verification s
Modeling and simulation of drug disposition has emerged as an important tool in drug development, clinical study design and regulatory review, and the number of physiologically based pharmacokineticExpand
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TLDR
This Review highlights prodrug design strategies for improved formulation and pharmacokinetic and targeting properties, with a focus on the most recently marketed prodrugs. Expand
Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers
TLDR
These findings support drug dispositional interactions between ethanol and MPH as dominant over potential biopharmaceutical considerations and Understanding the pharmacology underlying the frequent coabuse of MPH-ethanol provides rational guidance in the selection of first-line pharmacotherapy for comorbid attention-deficit/hyperactivity disorder–alcohol use disorder. Expand
Highly sensitive and selective detection of human carboxylesterase 1 activity by liquid chromatography with fluorescence detection.
  • D. Wang, Q. Jin, +8 authors L. Yang
  • Chemistry, Medicine
  • Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
  • 2016
TLDR
The newly developed LC-FD method was successfully applied to measure hCE1 activity in human liver preparations from individual donors (n=12), as well as in homogenates from eleven different human cell lines, which are very helpful for the deep understanding of the expression and function of h CE1 in human biological samples. Expand
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