Application of Model-Informed Drug Development in Dose Selection and Optimization for siRNA Therapies
In conclusion, the integration of MIDD offers substantial advantages in navigating the complex challenges of dose selection and optimization in siRNA drug development, which in turn accelerates the development process, supports regulatory decision making, and ultimately improves the clinical outcomes of siRNA-based therapies, fostering advancements in precision medicine across a diverse range of diseases.PMID:38426370 | DOI:10.1002/jcph.2418 (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Authors: Ye Yuan Liang Li Justin Earp Lian Ma Venkatesh Atul Bhattaram Vishnu Sharma Alexander Tong Yaning Wang Jiang Liu Hao Zhu Source Type: research

Effect of Age, Comedications, and CYP3A4/5 Polymorphisms on Perampanel Exposure in Chinese Pediatric Patients With Epilepsy
J Clin Pharmacol. 2024 Feb 21. doi: 10.1002/jcph.2415. Online ahead of print.ABSTRACTPerampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected in a tertiary children's hospital medical records system from January 2021 to December 2022. The influence factors on the daily dose, plasma...
Source: The Journal of Clinical Pharmacology - February 21, 2024 Category: Drugs & Pharmacology Authors: Huijuan Wang Junyan Wang Bin Lin Huifen Zhang Yangyang Sun Yuanyuan Wu Weifeng Ye Jing Miao Source Type: research

Effect of Age, Comedications, and CYP3A4/5 Polymorphisms on Perampanel Exposure in Chinese Pediatric Patients With Epilepsy
J Clin Pharmacol. 2024 Feb 21. doi: 10.1002/jcph.2415. Online ahead of print.ABSTRACTPerampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected in a tertiary children's hospital medical records system from January 2021 to December 2022. The influence factors on the daily dose, plasma...
Source: The Journal of Clinical Pharmacology - February 21, 2024 Category: Drugs & Pharmacology Authors: Huijuan Wang Junyan Wang Bin Lin Huifen Zhang Yangyang Sun Yuanyuan Wu Weifeng Ye Jing Miao Source Type: research

Effect of Age, Comedications, and CYP3A4/5 Polymorphisms on Perampanel Exposure in Chinese Pediatric Patients With Epilepsy
J Clin Pharmacol. 2024 Feb 21. doi: 10.1002/jcph.2415. Online ahead of print.ABSTRACTPerampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected in a tertiary children's hospital medical records system from January 2021 to December 2022. The influence factors on the daily dose, plasma...
Source: The Journal of Clinical Pharmacology - February 21, 2024 Category: Drugs & Pharmacology Authors: Huijuan Wang Junyan Wang Bin Lin Huifen Zhang Yangyang Sun Yuanyuan Wu Weifeng Ye Jing Miao Source Type: research

Effect of Age, Comedications, and CYP3A4/5 Polymorphisms on Perampanel Exposure in Chinese Pediatric Patients With Epilepsy
J Clin Pharmacol. 2024 Feb 21. doi: 10.1002/jcph.2415. Online ahead of print.ABSTRACTPerampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected in a tertiary children's hospital medical records system from January 2021 to December 2022. The influence factors on the daily dose, plasma...
Source: The Journal of Clinical Pharmacology - February 21, 2024 Category: Drugs & Pharmacology Authors: Huijuan Wang Junyan Wang Bin Lin Huifen Zhang Yangyang Sun Yuanyuan Wu Weifeng Ye Jing Miao Source Type: research

Effect of Age, Comedications, and CYP3A4/5 Polymorphisms on Perampanel Exposure in Chinese Pediatric Patients With Epilepsy
J Clin Pharmacol. 2024 Feb 21. doi: 10.1002/jcph.2415. Online ahead of print.ABSTRACTPerampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected in a tertiary children's hospital medical records system from January 2021 to December 2022. The influence factors on the daily dose, plasma...
Source: The Journal of Clinical Pharmacology - February 21, 2024 Category: Drugs & Pharmacology Authors: Huijuan Wang Junyan Wang Bin Lin Huifen Zhang Yangyang Sun Yuanyuan Wu Weifeng Ye Jing Miao Source Type: research

Effect of Age, Comedications, and CYP3A4/5 Polymorphisms on Perampanel Exposure in Chinese Pediatric Patients With Epilepsy
J Clin Pharmacol. 2024 Feb 21. doi: 10.1002/jcph.2415. Online ahead of print.ABSTRACTPerampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected in a tertiary children's hospital medical records system from January 2021 to December 2022. The influence factors on the daily dose, plasma...
Source: The Journal of Clinical Pharmacology - February 21, 2024 Category: Drugs & Pharmacology Authors: Huijuan Wang Junyan Wang Bin Lin Huifen Zhang Yangyang Sun Yuanyuan Wu Weifeng Ye Jing Miao Source Type: research

Effect of Age, Comedications, and CYP3A4/5 Polymorphisms on Perampanel Exposure in Chinese Pediatric Patients With Epilepsy
J Clin Pharmacol. 2024 Feb 21. doi: 10.1002/jcph.2415. Online ahead of print.ABSTRACTPerampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected in a tertiary children's hospital medical records system from January 2021 to December 2022. The influence factors on the daily dose, plasma...
Source: The Journal of Clinical Pharmacology - February 21, 2024 Category: Drugs & Pharmacology Authors: Huijuan Wang Junyan Wang Bin Lin Huifen Zhang Yangyang Sun Yuanyuan Wu Weifeng Ye Jing Miao Source Type: research

A Real-World Pharmacovigilance Study of Ceftazidime/Avibactam: Data Mining of the Food and Drug Administration Adverse Event Reporting System Database
J Clin Pharmacol. 2024 Feb 20. doi: 10.1002/jcph.2420. Online ahead of print.ABSTRACTCeftazidime/avibactam (CAZ/AVI) is a combination of a well-known third-generation, broad-spectrum cephalosporin with a new beta-lactamase inhibitor that has been approved for the treatment of various infectious diseases (especially multidrug-resistant Gram-negative bacterial infections) by the Food and Drug Administration (FDA). The current study extensively assessed CAZ/AVI-related adverse events (AEs) in the real world through data mining of the FDA Adverse Event Reporting System (FAERS) database to better understand toxicities. The sign...
Source: The Journal of Clinical Pharmacology - February 20, 2024 Category: Drugs & Pharmacology Authors: Haiping Yao Yanyan Wang Yan Peng Zhixiong Huang Guoping Gan Zhu Wang Source Type: research

A Real-World Pharmacovigilance Study of Ceftazidime/Avibactam: Data Mining of the Food and Drug Administration Adverse Event Reporting System Database
J Clin Pharmacol. 2024 Feb 20. doi: 10.1002/jcph.2420. Online ahead of print.ABSTRACTCeftazidime/avibactam (CAZ/AVI) is a combination of a well-known third-generation, broad-spectrum cephalosporin with a new beta-lactamase inhibitor that has been approved for the treatment of various infectious diseases (especially multidrug-resistant Gram-negative bacterial infections) by the Food and Drug Administration (FDA). The current study extensively assessed CAZ/AVI-related adverse events (AEs) in the real world through data mining of the FDA Adverse Event Reporting System (FAERS) database to better understand toxicities. The sign...
Source: The Journal of Clinical Pharmacology - February 20, 2024 Category: Drugs & Pharmacology Authors: Haiping Yao Yanyan Wang Yan Peng Zhixiong Huang Guoping Gan Zhu Wang Source Type: research

Mechanistic Modeling of Empagliflozin: Predicting Pharmacokinetics, Urinary Glucose Excretion, and Investigating Compensatory Role of SGLT1 in Renal Glucose Reabsorption
J Clin Pharmacol. 2024 Feb 16. doi: 10.1002/jcph.2413. Online ahead of print.ABSTRACTThe aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding...
Source: The Journal of Clinical Pharmacology - February 16, 2024 Category: Drugs & Pharmacology Authors: Xian Ping Guopeng Wang Dongmei Gao Source Type: research

Mechanistic Modeling of Empagliflozin: Predicting Pharmacokinetics, Urinary Glucose Excretion, and Investigating Compensatory Role of SGLT1 in Renal Glucose Reabsorption
J Clin Pharmacol. 2024 Feb 16. doi: 10.1002/jcph.2413. Online ahead of print.ABSTRACTThe aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding...
Source: The Journal of Clinical Pharmacology - February 16, 2024 Category: Drugs & Pharmacology Authors: Xian Ping Guopeng Wang Dongmei Gao Source Type: research

Mechanistic Modeling of Empagliflozin: Predicting Pharmacokinetics, Urinary Glucose Excretion, and Investigating Compensatory Role of SGLT1 in Renal Glucose Reabsorption
J Clin Pharmacol. 2024 Feb 16. doi: 10.1002/jcph.2413. Online ahead of print.ABSTRACTThe aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding...
Source: The Journal of Clinical Pharmacology - February 16, 2024 Category: Drugs & Pharmacology Authors: Xian Ping Guopeng Wang Dongmei Gao Source Type: research

Mechanistic Modeling of Empagliflozin: Predicting Pharmacokinetics, Urinary Glucose Excretion, and Investigating Compensatory Role of SGLT1 in Renal Glucose Reabsorption
J Clin Pharmacol. 2024 Feb 16. doi: 10.1002/jcph.2413. Online ahead of print.ABSTRACTThe aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding...
Source: The Journal of Clinical Pharmacology - February 16, 2024 Category: Drugs & Pharmacology Authors: Xian Ping Guopeng Wang Dongmei Gao Source Type: research

Neonatal Therapeutics: Time for a More Effective and Impactful Collaboration Between Neonatologists and Clinical Pharmacologists
J Clin Pharmacol. 2024 Feb 14. doi: 10.1002/jcph.2417. Online ahead of print.NO ABSTRACTPMID:38356244 | DOI:10.1002/jcph.2417 (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - February 15, 2024 Category: Drugs & Pharmacology Authors: John N van den Anker Source Type: research