7 research outputs found
Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities
Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings
Sodium ferric gluconate complex in hemodialysis patients: Adverse reactions compared to placebo and iron dextran
Sodium ferric gluconate complex in hemodialysis patients: Adverse reactions compared to placebo and iron dextran.BackgroundParenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control.MethodsThis multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125mg over 10 minutes, and compared to placebo comprising bacteriostatic saline.ResultsA total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001.ConclusionSFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued
Design and Synthesis of Sulfamoyl Benzoic Acid Analogues with Subnanomolar Agonist Activity Specific to the LPA<sub>2</sub> Receptor
Lysophosphatidic
acid (LPA) is a growth factor-like mediator and
a ligand for multiple GPCR. The LPA<sub>2</sub> GPCR mediates antiapoptotic
and mucosal barrier-protective effects in the gut. We synthesized
sulfamoyl benzoic acid (SBA) analogues that are the first specific
agonists of LPA<sub>2</sub>, some with subnanomolar activity. We developed
an experimental SAR that is supported and rationalized by computational
docking analysis of the SBA compounds into the LPA<sub>2</sub> ligand-binding
pocket