Population PK and Semimechanistic PK/PD Modeling and Simulation of Relugolix Effects on Testosterone Suppression in Men with Prostate Cancer.

Relugolix, the first orally active, nonpeptide gonadotropin-releasing hormone receptor antagonist, is approved in the United States and the European Union for the treatment of adult patients with advanced prostate cancer. The recommended dosing regimen is a 360-mg loading dose followed by a 120-mg daily dose. Relugolix and testosterone concentration data and clinical information from two phase I studies, two phase II studies, and the phase III safety and efficacy study (HERO) were used to develop a population pharmacokinetic (PopPK) model and a semimechanistic population pharmacokinetic/pharmacodynamic (PopPK/PD) model that characterized relugolix exposure and its relationship to testosterone concentrations.

Artificial Intelligence and Machine Learning Applied at the Point of Care.

Introduction: The increasing availability of healthcare data and rapid development of big data analytic methods has opened new avenues for use of Artificial Intelligence (AI)- and Machine Learning (ML)-based technology in medical practice. However, applications at the point of care are still scarce.

Objective: Review and discuss case studies to understand current capabilities for applying AI/ML in the healthcare setting, and regulatory requirements in the US, Europe and China.

Sorafenib administered using a high-dose, pulsatile regimen in patients with advanced solid malignancies: a phase I exposure escalation study.

Background: (Pre)clinical evidence is accumulating that intermittent exposure to increased doses of protein kinase inhibitors may improve their treatment benefit. In this phase I trial, the safety of high-dose, pulsatile sorafenib was studied.

Patients And Methods: High-dose sorafenib was administered once weekly in exposure escalation cohorts according to a 3 + 3 design.

Food-effect study of nilotinib in chronic myeloid leukaemia (NiFo study): Enabling dose reduction and relief of treatment burden.

Objectives: Taking advantage of its food-dependent bioavailability, the present study investigated the effect of a reduced dose taken with real-life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients.

Methods: Nilotinib was taken fasted (300 mg BID, days 1-4) or with real-life meals (200 mg BID, days 5-11). Rich sampling (days 1, 3, 8, 11) allowed for non-compartmental PK analysis.

Bevacizumab for Intravitreal Injection: Impact of Sub-Visible Particles on the Shelf-Life of Repackaged Bevacizumab.

Bevacizumab (Avastin) is a humanized monoclonal antibody approved by the European Medicines Agency for the intravenous treatment of cancer. However, it is often used as an intravitreal injection for the treatment of macular degeneration or edema. For this purpose, bevacizumab is repackaged from glass vials into plastic syringes.