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Updated: Sep 8, 2025
Induction and Assessment of Levodopa-induced Dyskinesias in a Rat Model of Parkinson's Disease
Published on: October 14, 2021
Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in
Filip Bergquist1, Mats Ehrnebo2, Dag Nyholm2
1From the Department of Pharmacology (F.B., E.E.), University of Gothenburg; Neurology (F.B.), Sahlgrenska University Hospital, Göteborg; Department of Pharmaceutical Biosciences (M.E.), Uppsala University; Pharm Assist Sweden AB (M.E.), Uppsala; Department of Neuroscience (D.N.), Uppsala University; Department of Clinical Neurosciences (A.J., P.S.), Karolinska Institutet (A.J., P.S.), Solna; Department of Biomedical and Clinical Sciences (F.L., N.D.), Linköping University (F.L., N.D.); Neurology (P.O.), Department of Clinical Sciences, Lund University; CTC Clinical Trial Consultants AB (F.H.), Uppsala; and Dizlin Pharmaceuticals (L.B.) Gothenburg, Sweden. filip.bergquist@pharm.gu.se.
Background And Objectives:
Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease.
Methods:
A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations.
Results:
With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. 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.
Discussion:
It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
Trial Registration Information:
ClinicalTrials.gov identifier: NCT03419806. Registration first posted on February 5, 2018, first patient enrolled on February 16, 2018.
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