Levodopa remains the most effective treatment for Parkinson's disease and is 
considered the gold standard therapy. However, disease progression and changes 
in the gastrointestinal tract result in a declining window of treatment response 
in a majority of patients. Efforts have been made recently to improve levodopa 
bioavailability either by developing more effective oral formulations or by 
innovating routes of administration (intestinal infusion, transcutaneous or 
inhaled levodopa). IPX066 is a novel levodopa-carbidopa (LD/CD) oral formulation 
combining immediate-release (IR) and extended-release (ER) LD/CD recently 
approved in the USA and the EU. Levodopa-carbidopa intestinal gel (LCIG) is an 
approved therapy consisting of a suspension of levodopa and carbidopa infused 
directly into the proximal jejunum via a percutaneous endoscopic 
gastrojejunostomy (PEG-J) tube through a portable infusion pump. Ongoing studies 
are evaluating the 'accordion pill' (AP09004), an ER LD/CD formulation with 
gastroretentive properties. ND0612 is a proprietary liquid formulation of LD/CD 
that enables subcutaneous administration via a small patch-pump device, and 
CVT-301 is a levodopa inhalation powder with rapid onset of action; both are 
currently in active studies. Other novel formulations have been discontinued, 
including DM-1992, which is a bilayer formulation containing an IR LD/CD layer 
and an ER LD/CD layer with gastroretentive properties, and XP21279, a novel oral 
levodopa prodrug that is absorbed from the small and large intestine by 
high-capacity nutrient transporters expressed throughout the gastrointestinal 
system. ODM-101 is a new oral formulation of levodopa/carbidopa/entacapone that 
contains a higher amount of carbidopa (65 or 105 mg), but no active studies are 
underway. The current review aims to summarize the pharmacokinetic aspects, 
clinical efficacy, and potential adverse events of novel levodopa formulations 
currently available or under development.