Streamlining physiologically-based pharmacokinetic model design for intravenous delivery of nanoparticle drugs.

Physiologically-based pharmacokinetic (PBPK) modeling for nanoparticles elucidates the nanoparticle drug's disposition in the body and serves a vital role in drug development and clinical studies. This paper offers a systematic and tutorial-like approach to developing a model structure and writing distribution ordinary differential equations based on asking binary questions involving the physicochemical nature of the drug in question. Further, by synthesizing existing knowledge, we summarize pertinent aspects in PBPK modeling and create a guide for building model structure and distribution equations, optimizing nanoparticle and non-nanoparticle specific parameters, and performing sensitivity analysis and model validation.

Image-guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies.

While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug-loaded nanomaterials or monoclonal antibodies), which can experience challenges to effective delivery due to particle size-dependent diffusion barriers at the target site. As a result, disparity between therapeutic plasma kinetics and kinetics at the site of action may exist, highlighting the importance of target site concentration kinetics in determining the pharmacodynamic effects of macromolecular therapeutic agents.

Thoracoscopic repair for congenital diaphragmatic hernia: lessons from 45 cases.

Purpose: To describe the surgical technique, initial results, and overview indications of thoracoscopic repair of congenital diaphragmatic hernia (CDH).

Materials And Methods: A retrospective review was undertaken of patients with CDH who underwent thoracoscopic repair by the same surgeon from January 2001 to January 2005. Patients underwent surgery under general anesthesia.