Flavia Storelli
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27 Can pupillometry be used for CYP2D6 phenotyping in children treated with tramadol? Open
Introduction Following the contraindication of codeine use in children, an increase in the use of tramadol has been observed in pain management protocols. However, tramadol PK/PD are also influenced by CYP2D6 activity. Genotyping and pheno…
View article: Toward improved predictions of pharmacokinetics of transported drugs in hepatic impairment: Insights from the extended clearance model
Toward improved predictions of pharmacokinetics of transported drugs in hepatic impairment: Insights from the extended clearance model Open
Hepatic impairment (HI) moderately (10‐fold) for drugs that are also substrates of cytochrome P450 (CYP) 3A enzymes. Using the extended clearance model, through simulations, we identified the ratio of sinusoidal efflux clearance (CL) over …
Evaluation of Pupillometry for CYP2D6 Phenotyping in Children Treated with Tramadol Open
Following the contraindication of codeine use in children, increasing use of tramadol has been observed in pain management protocols. However, tramadol’s pharmacokinetics (PK) and pharmacodynamics are influenced by cytochrome P450 (CYP)2D6…
View article: Predicting changes in the pharmacokinetics of CYP3A‐metabolized drugs in hepatic impairment and insights into factors driving these changes
Predicting changes in the pharmacokinetics of CYP3A‐metabolized drugs in hepatic impairment and insights into factors driving these changes Open
Physiologically based pharmacokinetic models, populated with drug‐metabolizing enzyme and transporter (DMET) abundance, can be used to predict the impact of hepatic impairment (HI) on the pharmacokinetics (PK) of drugs. To increase confide…
View article: The next frontier in ADME science: Predicting transporter-based drug disposition, tissue concentrations and drug-drug interactions in humans
The next frontier in ADME science: Predicting transporter-based drug disposition, tissue concentrations and drug-drug interactions in humans Open
This is the accepted manuscript version of the work published in its final form as Storelli, F., Yin, M., Kumar, A. R., Ladumor, M. K., Evers, R., Chothe, P. P., Enogieru, O. J., Liang, X., Lai, Y., & Unadkat, J. D. (2022). The next fronti…
Successful Prediction of Human Fetal Exposure to P-Glycoprotein Substrate Drugs Using the Proteomics-Informed Relative Expression Factor Approach and PBPK Modeling and Simulation Open
Many women take drugs during their pregnancy to treat a variety of clinical conditions. To optimize drug efficacy and reduce fetal toxicity, it is important to determine or predict fetal drug exposure throughout pregnancy. Previously, we d…
Successful Prediction of Human Steady‐State Unbound Brain‐to‐Plasma Concentration Ratio of P‐gp Substrates Using the Proteomics‐Informed Relative Expression Factor Approach Open
In order to optimize central nervous system (CNS) drug development, accurate prediction of the drug’s human steady‐state unbound brain interstitial fluid‐to‐plasma concentration ratio (K p,uu,brain ) is critical, especially for drugs that …
Abundance of P‐Glycoprotein and Other Drug Transporters at the Human Blood‐Brain Barrier in Alzheimer’s Disease: A Quantitative Targeted Proteomic Study Open
The human blood‐brain barrier (BBB) transporter P‐gp can efflux amyloid‐β (Aβ) out of the central nervous system (CNS). Aβ is thought to be the causative agent for Alzheimer’s disease (AD). Using positron emission tomography imaging, we ha…
Physiologically‐Based Pharmacokinetic Modeling for the Prediction of CYP2D6‐Mediated Gene–Drug–Drug Interactions Open
The aim of this work was to predict the extent of Cytochrome P450 2D6 (CYP2D6)‐mediated drug–drug interactions (DDIs) in different CYP2D6 genotypes using physiologically‐based pharmacokinetic (PBPK) modeling. Following the development of a…
P83 CYP2D6 phenotyping in children treated with tramadol at the Emergency Department Open
Background Pain management is essential and opioids side effects are of major concern. Tramadol safety and efficacy is influenced by CYP2D6 activity. Phenotyping measurement is available to assess CYP2D6 activity and allow a safe precision…
Genotype‐sensitive reversible and time‐dependent <span>CYP</span>2D6 inhibition in human liver microsomes Open
Cytochrome P450 ( CYP ) 2D6 metabolizes a wide range of xenobiotics and is characterized by a huge interindividual variability. A recent clinical study highlighted differential magnitude of CYP inhibition as a function of CYP 2D6 genotype.…
Understanding and predicting the association of intrinsic and extrinsic factors of pharmacokinetic variability in the context of precision medicine: impact of genetic polymorphisms on CYP2D6-mediated drug-drug interactions Open
La variabilité pharmacocinétique est une source majeure de variabilité de réponse aux médicaments, via notamment le métabolisme des médicaments par les cytochromes P450 (CYP). Parmi ceux-ci, le CYP2D6 représente un intérêt clinique considé…
The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation Open
Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing H…