L-Dopa pharmacokinetic profile with effervescent Melevodopa/Carbidopa versus standard-release Levodopa/Carbidopa tablets in Parkinson's disease: A Randomised study

Objectives. to characterize the pharmacokinetic profile of levodopa (l-dopa) and carbidopa after repeated doses of the effervescent tablet of melevodopa/carbidopa (v1512; sirio) compared with standard-release l-dopa/carbidopa in patients with fluctuating parkinson's disease. few studies assessed the pharmacokinetics of carbidopa to date. methods. this was a single-centre,randomized,double-blind,double-dummy,two-period crossover study. patients received v1512 (melevodopa 100 mg/carbidopa 25 mg) or l-dopa 100 mg/carbidopa 25 mg,7 doses over 24 hours (cohort 1),4 doses over 12 hours (cohort 2),or 2 doses over 12 hours in combination with entacapone 200 mg (cohort 3). pharmacokinetic parameters included area under the plasma-concentration time curve (auc),maximum plasma concentration (c m a x),and time to c m a x (t m a x). results. twenty-five patients received at least one dose of study medication. l-dopa absorption tended to be quicker and pharmacokinetic parameters less variable after v1512 versus l-dopa/carbidopa,both over time and between patients. accumulation of l-dopa in plasma was less noticeable with v1512. carbidopa exposure and interpatient variability was lower when v1512 or l-dopa/carbidopa was given in combination with entacapone. both treatments were well tolerated. conclusions. v1512 provides a more reliable l-dopa pharmacokinetic profile versus standard-release l-dopa/carbidopa,with less drug accumulation and less variability. this trial is registered with clinicaltrials.gov nct00491998. © 2015 fabrizio stocchi et al.