%0 Journal Article
%T Levodopa©\carbidopa intestinal gel high concentration formulation is clinically bioequivalent to commercial formulation
%A Charles Locke
%A Dilraj Sidhu
%A Hari V. Kalluri
%A Janet Benesh
%A Jian©\Hwa Han
%A Matthew Rosebraugh
%A Wei Liu
%J Archive of "Pharmacology Research & Perspectives".
%D 2019
%R 10.1002/prp2.473
%X 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 4.5) operating at 25 RPM. A single dose, open©\label study was conducted according to a two©\period, randomized, crossover design in 28 healthy subjects. The point estimate (PE) of the levodopa C max geometric mean for the LCIG©\HV formulation was 4% higher than that of the LCIG©\LV formulation. PEs of levodopa AUC t and AUC inf geometric means were comparable for both formulations. PEs of carbidopa C max, AUC t and AUC inf geometric means for the LCIG©\HV formulation were 3%©\5% higher than those of the LCIG©\LV formulation. For both formulations, the median T max for levodopa was 1.0 and 3.0 hours for carbidopa. The levodopa half©\life harmonic mean was 1.6 hour for both formulations. The carbidopa half©\life harmonic mean was 1.9 and 2.0 hour, respectively, for the LCIG©\HV and LCIG©\LV formulations. C max, AUC t and AUC inf of LD/CD carbidopa were comparable for both formulations. The current study demonstrates that the LCIG©\LV and LCIG©\HV formulations are clinically bioequivalent for LD/CD according to FDA guidance. However, the dissolution method was over discriminatory of formulation differences
%K bioequivalent
%K carbidopa
%K intestinal gel
%K levodopa
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452870/