CCR 20th Anniversary Commentary: Determining a Pharmacokinetic/Pharmacodynamic Relationship for Sunitinib—A Look Back.

The article by Mendel and colleagues, published in the January 1, 2003, issue of Clinical Cancer Research, described their novel preclinical approach to developing a thorough understanding of the exposure-activity relationship for sunitinib, a multitargeted receptor tyrosine kinase inhibitor being developed for oncology therapy. This work successfully set exposure guidelines to identify a biologically active dose in early clinical trials.

Evaluation of the potential for pharmacokinetic and pharmacodynamic interactions between dutogliptin, a novel DPP4 inhibitor, and metformin, in type 2 diabetic patients.

Objective: Dutogliptin is a novel, orally available, potent, and selective DPP4 inhibitor that improves glycemic control in type 2 diabetic patients. The objective of this study was to evaluate the potential pharmacokinetic and pharmacodynamic interactions, as well as the tolerability, of dutogliptin and metformin alone and in combination in type 2 diabetic patients.

Methods: This was a single-center, randomized, open-label, 3-way, crossover study in type 2 diabetic patients.

Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12-week, double-blind, randomized, placebo-controlled, multicentre trial.

Aim: To determine efficacy and tolerability of dutogliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, in patients with type 2 diabetes mellitus.

Methods: This was a 12-week, multicentre, randomized, double-blind, placebo-controlled trial in 423 patients with type 2 diabetes with suboptimal metabolic control. Following a 2-week single-blind placebo run-in, patients aged 18-75 years with a body mass index of 25-48 kg/m(2) and baseline HbA1c of 7.

The dipeptidyl peptidase-4 inhibitor PHX1149 improves blood glucose control in patients with type 2 diabetes mellitus.

Aim: To determine the efficacy and tolerability of PHX1149, a novel dipeptidyl peptidase-4 (DPP4) inhibitor, in patients with type 2 diabetes.

Methods: This is a multicentre, randomized, double-blind, placebo-controlled, 4-week study in patients with type 2 diabetes with suboptimal metabolic control. Patients with a baseline haemoglobin A(1c) (HbA(1c)) of 7.

Pharmacokinetic and pharmacodynamic assessments of the dipeptidyl peptidase-4 inhibitor PHX1149: double-blind, placebo-controlled, single- and multiple-dose studies in healthy subjects.

Background: PHX1149 is a dipeptidyl peptidase-4 (DPP4) inhibitor that is currently in clinical development for the treatment of type 2 diabetes mellitus. PHX1149 is a small (molecular weight = 241.16 Da), highly water-soluble (>2 g/mL), orally active molecule with a selectivity index of 15- to 319-fold relative to those of other members of the DPP family.