Bioavailability studies of oral dosage forms containing levodopa and carbidopa using column-switching chromatography followed by electrochemical detection

A reliable multi-dimensional column chromatographic method employing ampero metric detection using a carbon fibre microelectrode procedure was used for monitoring the plasma profiles and to evaluate the pharmacokinetics and bi oavailability of levodopa (l-dopa) and carbidopa (C-dopa), after ingestion of oral formulations containing these drugs. The peak currents obtained for the different analytes were directly proportional to the analyte over the concentration range 0.02-4 mu g ml(-1). Using this method, the minimum dete ctable concentration was estimated to be 5 and 8 ng ml(-1) for l-dopa and C -dopa, respectively. Recovery studies ranged from 93.83 to 89.76%, with a r elative standard deviation of less than 7%. The study was carried out in tw o separate weeks on five healthy non-patient fasted male/female volunteers in the age range 20-37 years and weighing between 60 kg and 78 kg. The phar macokinetic profile of two controlled-release products containing both l-do pa and C-dopa (Sinemet CR3 and CR4) was compared on the one hand and Sineme t conventional tablets on the other. The pharmacokinetic parameters, peak c oncentration (C (max)), the time taken to obtain this level (T-max), elimin ation half-time T-1/2, elimination rate constant (K-el), plasma level ratio , fluctuation index (FI) and the area under the time-concentration curve (A UC(0-8)), were investigated for each individual formulation. A comparison o f the uptake of l-dopa from the conventional formulation showed that l-dopa entered the plasma and achieved peak levels higher than that of the contro lled release formulations. However, it showed a much higher fluctuation ind ex and the plasma concentrations were more stable with the controlled relea se formulations. The data also indicated a very low accumulation of both le vodopa and carbidopa following repeated administration of the drugs, which was consistent with their relatively short half-lives (less than 2 h). In c ontrast, the half-life for the metabolite 3-orthomethyl dopa (3-OMD) is in the order of 13 h. As a result, there was an extensive accumulation of 3-OM D and its levels were significantly higher than those of levodopa or carbid opa upon repeated administration. Urine recoveries of the three analytes ov er one 8 h dosing interval showed that the majority of the excreted levodop a and carbidopa was recovered during the first 4 h, and there is proportion ally greater excretion of the carbidopa dose than the levodopa dose.