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

被引:22
作者
Sagar, KA [1 ]
Smyth, MR [1 ]
机构
[1] Dublin City Univ, Sch Chem Sci, Dublin 9, Ireland
关键词
D O I
10.1039/a906364a
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
A reliable multi-dimensional column chromatographic method employing amperometric detection using a carbon fibre microelectrode procedure was used for monitoring the plasma profiles and to evaluate the pharmacokinetics and bioavailability 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 detectable 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 relative standard deviation of less than 7%. The study was carried out in two 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 pharmacokinetic profile of two controlled-release products containing both l-dopa and C-dopa (Sinemet CR3 and CR4) was compared on the one hand and Sinemet conventional tablets on the other. The pharmacokinetic parameters, peak concentration (C (max)), the time taken to obtain this level (T-max), elimination half-time T-1/2, elimination rate constant (K-el), plasma level ratio, fluctuation index (FI) and the area under the time-concentration curve (AUC(0-8)), were investigated for each individual formulation. A comparison of 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 controlled release formulations. However, it showed a much higher fluctuation index and the plasma concentrations were more stable with the controlled release formulations. The data also indicated a very low accumulation of both levodopa and carbidopa following repeated administration of the drugs, which was consistent with their relatively short half-lives (less than 2 h). In contrast, 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-OMD and its levels were significantly higher than those of levodopa or carbidopa upon repeated administration. Urine recoveries of the three analytes over one 8 h dosing interval showed that the majority of the excreted levodopa and carbidopa was recovered during the first 4 h, and there is proportionally greater excretion of the carbidopa dose than the levodopa dose.
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页码:439 / 445
页数:7
相关论文
共 34 条
[1]  
BELLO P, 1988, J CHROMATOGR, V459, P341
[2]   EFFECT OF SUPPLEMENTAL CARBIDOPA ON BIOAVAILABILITY OF L-DOPA [J].
CEDARBAUM, JM ;
KUTT, H ;
DHAR, AK ;
WATKINS, S ;
MCDOWELL, FH .
CLINICAL NEUROPHARMACOLOGY, 1986, 9 (02) :153-159
[3]  
CEDERBAUM JM, 1987, CLIN PHARMACOKINET, V13, P141
[4]   ON-OFF PHENOMENA RELATED TO HIGH PLASMA LEVODOPA [J].
CLAVERIA, LE ;
CALNE, DB ;
ALLEN, JG .
BRITISH MEDICAL JOURNAL, 1973, 2 (5867) :641-643
[5]  
CURRY S, 1980, DRUG DISPOSITION PHA, P182
[6]   DETERMINATION OF L-DOPA AND 3-O-METHYL DOPA IN HUMAN-PLASMA BY EXTRACTION USING C-18 CARTRIDGES FOLLOWED BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ANALYSIS WITH ELECTROCHEMICAL DETECTION [J].
GERLACH, M ;
KLAUNZER, N ;
PRZUNTEK, H .
JOURNAL OF CHROMATOGRAPHY, 1986, 380 (02) :379-385
[7]  
GIBALDI M, 1991, BIOPHARMACEUTICS CLI, P4
[8]   ANALYSIS OF BROMACIL, DIURON AND 3,4-DICHLOROANILINE IN CONTAMINATED WELL WATER, USING A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC COLUMN-SWITCHING PROCEDURE [J].
GOEWIE, CE ;
HOGENDOORN, EA .
JOURNAL OF CHROMATOGRAPHY, 1987, 410 (01) :211-216
[9]   PRECOLUMN CLEANUP AND LIQUID-CHROMATOGRAPHIC DETERMINATION OF RESIDUES OF N-METHYLCARBAMATE PESTICIDES IN EXTRACTS OF TOTAL DIET [J].
GOEWIE, CE ;
HOGENDOORN, EA .
JOURNAL OF CHROMATOGRAPHY, 1987, 404 (02) :352-358
[10]   THE PHARMACOKINETICS OF INTRAVENOUS AND ORAL LEVODOPA IN PATIENTS WITH PARKINSONS-DISEASE WHO EXHIBIT ON-OFF FLUCTUATIONS [J].
HARDIE, RJ ;
MALCOLM, SL ;
LEES, AJ ;
STERN, GM ;
ALLEN, JG .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1986, 22 (04) :429-436