Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease.

Objective: The aim was to demonstrate that continuous s.c. infusion of a soluble levodopa (LD)/carbidopa (CD) phosphate prodrug combination effectively delivers stable LD exposure via a minimally invasive and convenient mode and has the potential to treat Parkinson's disease (PD) patients who are not well controlled on oral medication.

A hydrophobicity scale for the lipid bilayer barrier domain from peptide permeabilities: nonadditivities in residue contributions.

Passive peptide transport across lipid membranes is governed by the energetics of partitioning into the ordered chain interior coupled with the rate of diffusion across this region. A hydrophobicity scale for peptide transfer into the barrier region of membranes derived from permeability coefficients would be useful to predict passive permeation of peptides across biomembranes and for determining the thermodynamics of peptide/protein insertion into the membrane interior. This study reports transport rates across large unilamellar vesicles (LUVs) composed of egg lecithin at 25 degrees C for a series of peptides having the general structure N-p-toluyl-(X)(n) (n =1-3), where X is glycine, alanine, or sarcosine.

Transport across 1,9-decadiene precisely mimics the chemical selectivity of the barrier domain in egg lecithin bilayers.

The barrier domain solubility-diffusion theory of lipid bilayer permeability relates the permeability coefficient (P(m)) to the solute's partition coefficient (PC(barrier/w)) and diffusion coefficient (D(barrier)) in the ordered chain region of the bilayer that serves as the barrier region for polar permeants. To select the best solvent to mimic the barrier domain, permeability coefficients across a layer of 1,9-decadiene were compared with permeability coefficients from bilayer transport. Rate constants for transport, k, of alpha-methyl substituted analogues of p-toluic and p-methylhippuric acid were measured across a layer of 1,9-decadiene embedded in a PTFE filter membrane placed between two aqueous solutions in side-by-side diffusion cells.