A Minimal PBPK Model for Plasma and Cerebrospinal Fluid Pharmacokinetics of Trastuzumab after Intracerebroventricular Administration in Patients with HER2-Positive Brain Metastatic Localizations
ConclusionContinuous icv infusion of trastuzumab at 1.0  mg/h could be an alternative dosing regimen to rapidly achieve intraventricular CSF therapeutic concentrations. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 11, 2023 Category: Drugs & Pharmacology Source Type: research

Industry Perspective – What does Industry Need to Accelerate Drug Product and Process Development?
(Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 11, 2023 Category: Drugs & Pharmacology Source Type: research

Mechanistic Static Model based Prediction of Transporter Substrate Drug-Drug Interactions Utilizing Atorvastatin and Rifampicin
ConclusionsThis study demonstrates the effective application of a RAF-based translation method combined with mechanistic static modeling for transporter substrate DDI predictions and subsequent mechanistic interpretation. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 11, 2023 Category: Drugs & Pharmacology Source Type: research

Cortisol as Biomarker for CYP17-Inhibition is Associated with Therapy Outcome of Abiraterone Acetate
ConclusionOur study shows that cortisol is not an independent predictor of abiraterone response in patients with mCRPC, but it is of added value in combination with abiraterone levels, to predict a response on abiraterone. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 11, 2023 Category: Drugs & Pharmacology Source Type: research

Assessing Dose-Exposure –Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach
ConclusionsThe mechanistic PBPK model suggested that the higher fraction of unbound miltefosine in plasma was responsible for a higher probability of failure in paediatrics because of the difference in the distribution of plasma proteins between adults and paediatrics. The developed PBPK models could be used to determine an optimal miltefosine dose regime in future clinical trials.Graphical Abstract (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 10, 2023 Category: Drugs & Pharmacology Source Type: research

Application of NMR and Chemometric Analyses to Better Understand the Quality Attributes in pH and Thermally Degraded Monoclonal Antibodies
ConclusionThe chemometric analyses support the lack of statistical differences in the structure of pH-thermal stressed adalimumab, however, it reveals conformational changes or chemical modifications in trastuzumab after forced degradation. Application of chemometrics in comparative NMR studies enables HOS characterization and showcases the sensitivity and specificity in detecting differences in the spectra of mAbs after pH-thermal forced degradation with respect to local and global protein structure. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 5, 2023 Category: Drugs & Pharmacology Source Type: research

Preclinical Pharmacokinetics and Translational Pharmacokinetic/Pharmacodynamic Modeling of M8891, a Potent and Reversible Inhibitor of Methionine Aminopeptidase 2
ConclusionThe defined target PK and PD levels supported the design of the clinical Phase Ia dose escalation study of M8891 (NCT03138538) and selection of the recommended Phase II dose. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 5, 2023 Category: Drugs & Pharmacology Source Type: research

Application of NMR and Chemometric Analyses to Better Understand the Quality Attributes in pH and Thermally Degraded Monoclonal Antibodies
ConclusionThe chemometric analyses support the lack of statistical differences in the structure of pH-thermal stressed adalimumab, however, it reveals conformational changes or chemical modifications in trastuzumab after forced degradation. Application of chemometrics in comparative NMR studies enables HOS characterization and showcases the sensitivity and specificity in detecting differences in the spectra of mAbs after pH-thermal forced degradation with respect to local and global protein structure. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 5, 2023 Category: Drugs & Pharmacology Source Type: research

Preclinical Pharmacokinetics and Translational Pharmacokinetic/Pharmacodynamic Modeling of M8891, a Potent and Reversible Inhibitor of Methionine Aminopeptidase 2
ConclusionThe defined target PK and PD levels supported the design of the clinical Phase Ia dose escalation study of M8891 (NCT03138538) and selection of the recommended Phase II dose. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 5, 2023 Category: Drugs & Pharmacology Source Type: research

Development and Validation of Discriminatory In-vitro Release Method for Intramammary Drug Product
ConclusionThe developedin-vitro release methods can be used as a potential tool forin-vitro comparability evaluations for IMM formulations. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 3, 2023 Category: Drugs & Pharmacology Source Type: research

Physiological Dynamics in the Upper Gastrointestinal Tract and the Development of Gastrointestinal Absorption Models for the Immediate-Release Oral Dosage Forms in Healthy Adult Human
AbstractThis review is a revisit of various oral drug absorption models developed in the past decades, focusing on how to incorporate the physiological dynamics in the upper gastrointestinal (GI) tract. For immediate-release oral drugs, GI absorption is a critical input of drug exposure and subsequent human body response, yet difficult to model largely due to the complex GI environment. One of the biggest hurdles lies at capturing the high within-subject variability (WSV) of bioavailability measures, which can be mechanistically explained by the GI physiological dynamics. A thorough summary of how GI dynamics is handled in...
Source: Pharmaceutical Research - October 3, 2023 Category: Drugs & Pharmacology Source Type: research

Development and Validation of Discriminatory In-vitro Release Method for Intramammary Drug Product
ConclusionThe developedin-vitro release methods can be used as a potential tool forin-vitro comparability evaluations for IMM formulations. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 3, 2023 Category: Drugs & Pharmacology Source Type: research

Physiological Dynamics in the Upper Gastrointestinal Tract and the Development of Gastrointestinal Absorption Models for the Immediate-Release Oral Dosage Forms in Healthy Adult Human
AbstractThis review is a revisit of various oral drug absorption models developed in the past decades, focusing on how to incorporate the physiological dynamics in the upper gastrointestinal (GI) tract. For immediate-release oral drugs, GI absorption is a critical input of drug exposure and subsequent human body response, yet difficult to model largely due to the complex GI environment. One of the biggest hurdles lies at capturing the high within-subject variability (WSV) of bioavailability measures, which can be mechanistically explained by the GI physiological dynamics. A thorough summary of how GI dynamics is handled in...
Source: Pharmaceutical Research - October 3, 2023 Category: Drugs & Pharmacology Source Type: research

Practical Advice on Scientific Design of Freeze-Drying Process: 2023 Update
ConclusionsThe authors revisited advice from a seminal paper by Tang and Pikal (Pharm Res. 21(2):191-200, 2004) on selecting freeze-drying process conditions and found that the majority of recommendations are still applicable today. There have been a number of advancements, including methods to promote ice nucleation and computer modeling for all steps of freeze-drying process. The authors created a database for primary drying and provided examples of complete freeze-drying cycles design. The paper may supplement the knowledge of scientists and formulators and serve as a user-friendly tool for quickly estimating the design...
Source: Pharmaceutical Research - October 2, 2023 Category: Drugs & Pharmacology Source Type: research