Pharmaceutical research
-
Pharmaceutical research · Oct 2011
Multicenter StudyPopulation PK and IgE pharmacodynamic analysis of a fully human monoclonal antibody against IL4 receptor.
For AMG 317, a fully human monoclonal antibody to interleukin receptor IL-4Rα, we developed a population pharmacokinetic (PK) model by fitting data from four early phase clinical trials of intravenous and subcutaneous (SC) routes simultaneously, investigated important PK covariates, and explored the relationship between exposure and IgE response. ⋯ The population PK model adequately described AMG 317 PK from IV and SC routes over a 60-fold range of doses with two dosing strengths across multiple studies covering healthy volunteers and patients with mild to severe asthma. IgE response across a range of doses and over the sampling time points was found to be related to cumulative AMG 317 exposure.
-
Pharmaceutical research · Oct 2011
Mechanism-based pharmacokinetic-pharmacodynamic modeling of the dopamine D2 receptor occupancy of olanzapine in rats.
A mechanism-based PK-PD model was developed to predict the time course of dopamine D(2) receptor occupancy (D(2)RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. ⋯ This model includes both receptor binding kinetics and pharmacokinetics as the basis for the prediction of the D(2)RO in rats. Moreover, this modeling framework can be applied to scale the in vitro and preclinical information to clinical receptor occupancy.
-
Pharmaceutical research · Jun 2011
Combination of hyaluronic acid hydrogel scaffold and PLGA microspheres for supporting survival of neural stem cells.
To develop a biomaterial composite for promoting proliferation and migration of neural stem cells (NSCs), as well as angiogenesis on the materials, to rescue central nervous system (CNS) injuries. ⋯ Our created HA hydrogel/PLGA microsphere systems have a good potential for controlled delivery of varied biofactors and supporting NSCs for brain repair and implantation.
-
Pharmaceutical research · Feb 2011
A semi-mechanistic gastric emptying model for the population pharmacokinetic analysis of orally administered acetaminophen in critically ill patients.
To develop a semi-mechanistic population pharmacokinetic model based on gastric emptying function for acetaminophen plasma concentration in critically ill patients tolerant and intolerant to enteral nutrition before and after prokinetic therapy. ⋯ The four-compartment semi-mechanistic population pharmacokinetic model adequately described the data. The gastric emptying half-time is improved by a factor of about 20 in the patients that are intolerant to enteral nutrition after treatment with prokinetic agents.
-
Pharmaceutical research · Sep 2010
Evaluation of enhanced condensational growth (ECG) for controlled respiratory drug delivery in a mouth-throat and upper tracheobronchial model.
The objective of this study is to evaluate the effects of enhanced condensational growth (ECG), as a novel inhalation drug delivery method, on nano-aerosol deposition in a mouth-throat (MT) and upper tracheobronchial (TB) model using in vitro experiments and computational fluid dynamics (CFD) simulations. ⋯ The ECG platform appears to offer an effective method of delivering nano-aerosols through the extrathoracic region, with minimal deposition, to the tracheobronchial airways and beyond. Aerosol deposition is then facilitated as enhanced condensational growth increases particle size. Future studies will investigate the effects of physio-chemical drug properties and realistic inhalation profiles on ECG growth characteristics.