Intravenously and Subcutaneously Infused Levodopa/Carbidopa for Advanced Parkinson Disease

Pharmacokinetic findings from a study (NCT00660673) of intravenous levodopa/carbidopa (LCIV) (DIZ101; Dizlin Pharmaceuticals, Gothenburg, Sweden) or subcutaneous levodopa/carbidopa (LCSC) (DIZ102; Dizlin) vs intestinal levodopa/carbidopa gel infusion (LCIG) in people with advanced Parkinson disease (PD) has been published in Neurology.
After adjusting for estimated bioavailability, LCIV and LCSC infusions over 16 hours were bioequivalent to LCIG infusions. Carbidopa levels were higher with LCIV and LCSC because of poor uptake of LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of LCSC as with LCIG and remained stable throughout the infusions.

"The outcome shows that subcutaneous administration of a continuously buffered levodopa solution could be a feasible technique to safely and rapidly obtain high and stable levodopa levels in patients with PD", says principal investigator Filip Bergquist, MD, senior consultant in neurology and professor of pharmacology.

"The data were those that we had hoped for," says Björn Velin, chief executive officer of Dizlin Pharmaceuticals. "The results suggest that LCSC, administered by means of a portable twin pump, may serve as a levodopa/carbidopa monotherapy for patients requiring high levodopa levels but experience motor fluctuations when receiving oral administration. The rapid uptake of levodopa from the subcutaneous tissue would enable considerable flexibility in dosing, which we also regard as an important advantage. Unlike intestinal administration of a levodopa/carbidopa gel, (these formulations) require no surgery and display considerable room temperature stability prior to mixing."

The 3-period, cross-over, open-label, multicenter study compared the 3 formulations, each delivered for 16 hours, in participants (n=18) with PD who had been using LCIG as their regular treatment (600 mg carbidopa/4,000 mg levodopa per day) for at least 30 days before screening. Participant's Hoehn and Yahr scores were 3 or lower during LCIG infusion and their body mass index was between 18 kg/m2 and 35 kg/m2. All individuals receiving any of the treatments (n=20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient.