The FDA-approved drug label is the official description of a drug product and includes what the drug is used for, who should take it, side effects, instructions for use, and safety information for clinicians and patients. For drug companies, the label is the culmination of years of work and millions, if not billions of dollars. … Continued
This report describes a pharmacokinetic/pharmacodynamic model for pramlintide, an amylinomimetic, in type 1 diabetes mellitus (T1DM). Plasma glucose and drug concentrations were obtained following bolus and 2-h intravenous infusions of pramlintide at three dose levels or placebo in 25 T1DM subjects during the postprandial period in a crossover study. The original clinical data were reanalyzed … Continued
Dutogliptin is a selective dipeptidyl peptidase-4 inhibitor shown to be efficacious and safe in patients with type 2 diabetes mellitus (T2DM). Population pharmacokinetic (PK) analysis of dutogliptin was performed based on data collected in 561 healthy subjects and patients with T2DM enrolled in Phase I and II studies to assess sources of variability and support … Continued
The G-protein-coupled receptor 40 agonist (GPR40) TAK-875 is being developed as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Pharmacometric approaches such as model-based exposure-response and meta-analyses were applied to (i) characterize exposure/dose-efficacy responses of TAK-875, (ii) characterize the time course of glycosylated hemoglobin A1c (HbA1c) … Continued
The purpose of this analysis was to develop a population pharmacokinetic model for CS-917, an oral hypoglycemic prodrug, and its 3 metabolites. The population pharmacokinetic model was used to predict exposure of the active moiety R-125338 and thus to identify potential CS-917 dosage reduction criteria.
PF-04971729 is a potent, selective SGLT2i in development for treatment of type 2 diabetes mellitus (T2DM). Since there is growing recognition of the need for comparative effectiveness of various ADA, a model was developed to quantify time course of dose vs HbA1c response of PF-04971729 relative to other ADA including SGLT2i, DPP4 inhibitors (DPP4i), GLP-1 … Continued
PF-04971729 is a potent, selective SGLT2i in development for treatment of type 2 diabetes mellitus (T2DM). Since there is growing recognition of the need for comparative effectiveness of various ADA, a model was developed to quantify the time course of dose vs body weight change for PF-04971729 relative to other ADA including SGLT2i, DPP4 inhibitors … Continued
Fructose-1,6-biphophatase has been regarded as a novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). 3D-QSAR and docking studies were performed on a series of [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors. The CoMFA and CoMSIA models using thirty-seven molecules in the training set gave rcv2 values of 0.614 and 0.598, r2 values … Continued
Weight loss outcomes achieved through conventional behavior change interventions are prone to deterioration over time. Basic learning laboratory studies in the area of behavioral extinction and renewal and multilevel models of weight control offer clues as to why newly acquired weight loss skills are prone to relapse.