Pharmacoscintigraphic and pharmacokinetic evaluation on healthy human volunteers of sustained-release floating minitablets containing levodopa and carbidopa.
In this study, scintigraphic and pharmacokinetic studies were conducted on 10 healthy, fed volunteers. Two concepts of sustained-release floating minitablets--Levo-Form 1 (matrix) and 2 (coated)--were evaluated and compared to the marketed product Prolopa HBS 125. All the floating forms were radiolabelled with (111)In in order to evaluate their gastric residence time using gamma-scintigraphy. It was shown that the three formulations offered almost the same mean gastric residence time, which was about 240 min. Prolopa HBS 125 and Levo-Form 2 presented intragastric disintegration, which can lead to a more pronounced "peak & valley" effect on the plasma concentration-time profile of levodopa. In contrast, the plasma concentration-time profile of levodopa following the administration of Levo-Form 1 was more evenly distributed. Moreover, Levo-Form 1 provided the lowest variations between men and women in terms of AUC and C(max) values. Finally, when the same amount of inhibitors of extracerebral dopa decarboxylase--carbidopa and benserazide--had been administrated, the mean AUC, C(max) and T(max) values obtained for benserazide were lower than those obtained for carbidopa.
Goole
J
J
Laboratoire de Pharmacie Galénique et Biopharmacie, Université Libre de Bruxelles, Campus de la Plaine, CP 207, Boulevard du Triomphe, 1050 Brussels, Belgium.
Van Gansbeke
B
B
Pilcer
G
G
Deleuze
Ph
P
Blocklet
D
D
Goldman
S
S
Pandolfo
M
M
Vanderbist
F
F
Amighi
K
K
D000328:Adult; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002230:Carbidopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006801:Humans; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D011208:Powders; D011877:Radionuclide Imaging; D013607:Tablets; D014018:Tissue Distribution; D055815:Young Adult
D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D007205:Indium Radioisotopes; D011208:Powders; D013607:Tablets; D007980:Levodopa; D002230:Carbidopa