Pharmacokinetics of Levodopa/Carbidopa Microtablets Versus Levodopa/Benserazide and Levodopa/Carbidopa in Healthy Volunteers
Clinical Neuropharmacology, 05/31/2012
Nyholm D et al. – The new levodopa/carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.Methods
- A single–dose, open, randomized, 3–way crossover study was performed in 19 healthy subjects.
- Concentrations of levodopa, carbidopa, and the metabolite 3–O–MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation.
- The LC–5 microtablets were bioequivalent to the LC–100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB–100 tablets in AUC.
- The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets.
- Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC–5/LC–100 for this compound did not reach the target.
- Nevertheless, comparison of 3–O–MD levels for LC–5/LC–100, assuming proportionality to levodopa levels, demonstrated bioequivalence.