CPT: Pharmacometrics and Systems Pharmacology 
This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.
This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.A physiologically ‐based pharmacokinetic/pharmacodynamic modeling approach for drug–drug‐gene interaction evaluation of S‐warfarin with fluconazole
This study provides a whole-body physiologically-based pharmacokinetic/PD (PBPK/PD) model of S-warfarin for predicting the effects of drug–drug−gene interactions on S-warfarin PKs and PDs. The PBPK/PD model of S-warfarin was developed in PK-Sim and MoBi. Drug-depende nt parameters were obtained from the literature or optimized. Of the 34 S-warfarin plasma concentration-time profiles used, 96% predicted plasma concentrations within twofold range compared to observed data. For S-warfarin plasma concentration-time profiles withCYP2C9 genotype, 364 of 386 predicted plasma concentration values (~94%) fell within the twofold...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 15, 2024 Category: Drugs & Pharmacology Authors: Kuo Geng,
Chaozhuang Shen,
Xiaohu Wang,
Xingwen Wang,
Wenxin Shao,
Wenhui Wang,
Tao Chen,
Hua Sun,
Haitang Xie Tags: ARTICLE Source Type: research
Physiologically based pharmacokinetic modeling of imatinib and N ‐desmethyl imatinib for drug–drug interaction predictions
AbstractThe first-generation tyrosine kinase inhibitor imatinib has revolutionized the development of targeted cancer therapy and remains among the frontline treatments, for example, against chronic myeloid leukemia. As a substrate of cytochrome P450 (CYP) 2C8, CYP3A4, and various transporters, imatinib is highly susceptible to drug –drug interactions (DDIs) when co-administered with corresponding perpetrator drugs. Additionally, imatinib and its main metaboliteN-desmethyl imatinib (NDMI) act as inhibitors of CYP2C8, CYP2D6, and CYP3A4 affecting their own metabolism as well as the exposure of co-medications. This work pr...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Authors: Helena Leonie Hanae Loer,
Christina Kovar,
Simeon R üdesheim,
Fatima Zahra Marok,
Laura Maria Fuhr,
Dominik Selzer,
Matthias Schwab,
Thorsten Lehr Tags: ARTICLE Source Type: research
Understanding CYP3A4 and P ‐gp mediated drug–drug interactions through PBPK modeling – Case example of pralsetinib
AbstractPralsetinib, a potent and selective inhibitor of oncogenic RET fusion and RET mutant proteins, is a substrate of the drug metabolizing enzyme CYP3A4 and a substrate of the efflux transporter P-gp based on in vitro data. Therefore, its pharmacokinetics (PKs) may be affected by co-administration of potent CYP3A4 inhibitors and inducers, P-gp inhibitors, and combined CYP3A4 and P-gp inhibitors. With the frequent overlap between CYP3A4 and P-gp substrates/inhibitors, pralsetinib is a challenging and repre sentative example of the need to more quantitatively characterize transporter-enzyme interplay. A physiologically...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Authors: Christine Bowman,
Michael Dolton,
Fang Ma,
Sravanthi Cheeti,
Denison Kuruvilla,
Rucha Sane,
Nastya Kassir,
Yuan Chen Tags: ARTICLE Source Type: research
Item response theory analysis of daytime sleepiness as a symptom of obstructive sleep apnea
AbstractObstructive sleep apnea (OSA) is a sleep disorder which is linked to many health risks. The gold standard to evaluate OSA in clinical trials is the Apnea-Hypopnea Index (AHI). However, it is time-consuming, costly, and disregards aspects such as quality of life. Therefore, it is of interest to use patient-reported outcomes like the Epworth Sleepiness Scale (ESS), which measures daytime sleepiness, as surrogate end points. We investigate the link between AHI and ESS, via item response theory (IRT) modeling. Through the developed IRT model it was identified that AHI and ESS are not correlated to any high degree and p...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 12, 2024 Category: Drugs & Pharmacology Authors: Gustaf J. Wellhagen,
Mats O. Karlsson,
Maria C. Kjellsson,
Dirk Garmann,
Astrid Br öker,
Yang Zhang,
Mika Nokela,
Gerrit Weimann,
Ashraf Yassen Tags: ARTICLE Source Type: research
Deep ‐NCA: A deep learning methodology for performing noncompartmental analysis of pharmacokinetic data
This study advances the application of DL to PK studies and introduces an effective method for handling sparse PK data. With further validation and refinement, Deep-NCA could significantly enhance the efficiency of drug development by providing more accurate NCA estimates while requiring fewer PK samples. (Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Gengbo Liu,
Logan Brooks,
John Canty,
Dan Lu,
Jin Y. Jin,
James Lu Tags: ARTICLE Source Type: research
Pharmacokinetics and exposure –safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit
AbstractCiprofol (HSK3486) is a newly developed, highly selective γ-aminobutyric acid-A (GABAA) receptor potentiator that is recently approved for a new indication of sedation for patients in the intensive care unit (ICU) in China. This analysis aimed to characterize the population pharmacokinetics (PopPKs) of ciprofol and evaluate the relationship of exposure with hypotension in mechanically ventilated patients in the ICU. A total of 462 subjects with 3918 concentration measurements from two clinical trials of mechanically ventilated patients in the ICU, four clinical trials of elective surgical patients, and six clinica...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 6, 2024 Category: Drugs & Pharmacology Authors: Lu Liu,
Kun Wang,
Zhongyi Sun,
Pangke Yan,
Mengyue Hu,
Xiao Liu,
Meixia Chen,
Nan Wu,
Xiaoqiang Xiang Tags: ARTICLE Source Type: research
Evaluation of covariate effects in item response theory models
We present a new method to investigate item-specific effects in IRT models, which is based on inspection of residuals. The method was investigated in a simulation exercise with a model for the Epworth Sleepiness Scale. We also provide a detailed discussion as a guidance on how to build a robust covariate IRT model. (Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - March 5, 2024 Category: Drugs & Pharmacology Authors: Gustaf J. Wellhagen,
Ashraf Yassen,
Dirk Garmann,
Astrid Br öker,
Alexander Solms,
Yang Zhang,
Maria C. Kjellsson,
Mats O. Karlsson Tags: ARTICLE Source Type: research
Development of a physiologically ‐based pharmacokinetic model to simulate the pharmacokinetics of intramuscular antiretroviral drugs
AbstractThere is growing interest in the use of long-acting (LA) injectable drugs to improve treatment adherence. However, their long elimination half-life complicates the conduct of clinical trials. Physiologically-based pharmacokinetic (PBPK) modeling is a mathematical tool that allows to simulate unknown clinical scenarios for LA formulations. Thus, this work aimed to develop and verify a mechanistic intramuscular PBPK model. The framework describing the release of a LA drug from the depot was developed by including both the physiology of the injection site and the physicochemical properties of the drug. The framework w...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 2, 2024 Category: Drugs & Pharmacology Authors: Sara Bettonte,
Mattia Berton,
Manuel Battegay,
Felix Stader,
Catia Marzolini Tags: ARTICLE Source Type: research
