Safety of Levodopa-Carbidopa Intestinal Gel Treatment in Patients with Advanced Parkinson's Disease Receiving ≥2000 mg Daily Dose of Levodopa.

Background: Levodopa-carbidopa intestinal gel (LCIG) provides continuous levodopa administration and clinical benefits to patients with advanced Parkinson's disease (PD). This report evaluates long-term safety and efficacy of high-dose LCIG in PD patients.

Methods: Data were collected from several prospective, phase III clinical studies and an observational registry.

AMPA receptor subunit localization in schizophrenia anterior cingulate cortex.

The glutamate hypothesis of schizophrenia suggests that altered glutamatergic transmission occurs in this illness, although precise mechanisms of dysregulation remain elusive. AMPA receptors (AMPARs), a subtype of ionotropic glutamate receptor, are the main facilitators of fast, excitatory neurotransmission in the brain, and changes in AMPAR number or composition at synapses can regulate synaptic strength and plasticity. Prior evidence of abnormal expression of transmembrane AMPAR regulatory proteins (TARPs) in schizophrenia suggests defective trafficking of AMPARs, which we propose could lead to altered AMPAR expression at excitatory synapses.

A post hoc comparison of levodopa-carbidopa intestinal gel daytime monotherapy vs polytherapy safety and efficacy in patients with advanced Parkinson's disease: Results from 6 phase 3/3b open-label studies.

Introduction: As Parkinson's disease (PD) progresses, the number/frequency of PD medications tend to increase, which is correlated with decreased patient compliance and suboptimal control of PD symptoms. We investigated efficacy and safety of levodopa-carbidopa intestinal gel (LCIG) daytime monotherapy (with or without nighttime oral levodopa-carbidopa) compared with polytherapy (LCIG with ≥1 adjunctive PD therapy) in advanced PD patients.

Methods: This post hoc descriptive study compared LCIG stable daytime monotherapy with LCIG stable polytherapy in all six phase 3/3b open-label studies from both US and international sites; because of study design variability, pooling data for comparison was not appropriate.

Levodopa-carbidopa intestinal gel high concentration formulation is clinically bioequivalent to commercial formulation.

A new levodopa-carbidopa intestinal gel (LCIG) system featuring a higher levodopa/carbidopa (LD/CD) concentration and viscosity, LCIG-HV, is being developed to reduce the intrajejunal volume of LD/CD that is administered as compared to the current commercial formulation, LCIG-LV. This study characterizes the LCIG-HV formulation and compares it to the LCIG-LV formulation via dissolution testing and a clinical pharmacokinetic bioequivalence study. In vitro release profiles of LD/CD were determined using a USP Dissolution Apparatus 2 with 500 mL of phosphate buffer (pH 4.

Long-term safety and efficacy of levodopa-carbidopa intestinal gel in advanced Parkinson's disease.

Background: Levodopa-carbidopa intestinal gel (designated as carbidopa-levodopa enteral suspension in the United States) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease patients through continuous delivery of levodopa via percutaneous endoscopic gastrojejunostomy. We report long-term safety and efficacy outcomes from an open-label phase 3 treatment program.

Methods: PD patients (n = 262) who completed a 12-week double-blind study and its 52-week open-label extension or a separate 54-week open-label study were enrolled in this ongoing phase 3 open-label, multinational study (NCT00660673).