The hydrosoluble fiber Plantago ovata husk improves levodopa (with carbidopa) bioavailability after repeated administration

Abstract

The influence of treatment duration (7 or 14 days) with Plantago ovata husk/levodopa/carbidopa in the bioavailability and other pharmacokinetic parameters of levodopa were evaluated in rabbits. Fiber was administered at two different doses, 100 and 400 mg/kg, and the dosage of levodopa/carbidopa was 20:5 mg/kg. These doses were administered once a day. When 100 mg/kg of fiber was administered, the mean AUC value obtained for levodopa increased 20.2% from day 1 to day 7, and 27.2% from day 1 to day 14; C max was 8.6% higher on day 7 and 11.7% higher on day 14. When administering 400 mg/kg of fiber, the increase in AUC values was 17.6% on day 7 and 24.9% on day 14, and that of C max 11.1% on day 7 and 11.3% on day 14. The concentration determined immediately before drug administration (C min ) increased progressively with the duration of treatment, and the highest increase (53.2%) was observed on day 14 with 100 mg/kg of fiber. There was also a delay in levodopa elimination (higher MRT and lower Cl) in a fiber-dose dependent manner. In summary, we found that there was an improvement in the extent of levodopa absorbed with higher final concentrations and that levodopa elimination was slower with the administration of P. ovata husk.

Effects ofPlantago ovataHusk on Levodopa (with Carbidopa) Bioavailability in Rabbits with Autonomic Gastrointestinal Disorders

“…If we compare the results of the present work with those obtained in another previous study (Diez et al, 2008) performed with administration of P. ovata husk (100 and 400 mg/kg) to rabbits with normal gastrointestinal peristalsis, we can see that on day 1 and after the administration of the low dose of fiber (100 mg/kg), AUC values were very similar (114.58 versus 112.65 g ⅐ min ⅐ ml Ϫ1 on day 1 of 7 and 119.14 versus 108.37 g ⅐ min ⅐ ml Ϫ1 on day 1 of 14) and C max values were lower (1.70 versus 2.02 g/ml on day 1 of 7 and 1.54 versus 2.03 g/ml on day 1 of 14). After 7 days of treatment, AUC (171.67 g ⅐ min ⅐ ml Ϫ1 ) was higher than that obtained in rabbits with normal gastrointestinal motility (141.30 g ⅐ min ⅐ ml Ϫ1 ), and C max was lower (2.03 versus 2.21 g/ml).…”

“…When this high dose of fiber was administered for the 14-day period, the mean values obtained for AUC when biperiden was not administered (Diez et al, 2008) were slightly higher on day 1 (125.50 versus 114.28 g ⅐ min ⅐ ml Ϫ1 ) and lower on day 14 (167.19 versus 182.44 g ⅐ min ⅐ ml Ϫ1 ). On the other hand, C max was lower in the presence of biperiden on days 1 (2.04 versus 1.50 g/ml) and 14 (2.26 versus 1.99 g/ml).…”

“…On day 14, the results were similar: C max was also lower (1.99 versus 2.30 g/ml) and AUC was higher (174.13 versus 148.79 g ⅐ min ⅐ ml Ϫ1 ) in the presence of biperiden and fiber. Regarding the use of 400 mg/kg P. ovata husk, the administration of the drugs to normal rabbits (Diez et al, 2008) yielded higher values FIG. 5.…”

“…Maximum plasma levodopa concentration (C max ) and the time to reach maximum concentration (t max ) were read directly from the individual plasma concentration-time curves. The fraction of levodopa absorbed [F (percent)] was calculated by dividing the mean AUC by the value of the mean intravenous AUC obtained in a previous study (Diez et al, 2008) after levodopa administration alone.…”

Oat fibre: overview on their main biological properties

“…Fibre administration can reduce the severity of dopamine-mediated gastrointestinal and cardiovascular adverse eVects by providing lower levodopa maximum concentrations and also provide a more uniform response by maintaining plasma concentrations in a narrower range, when levodopa was administered alone [23] and in the presence of carbidopa [20]. A further study showed that there was an improvement in the extent of levodopa absorbed with higher Wnal concentrations using repeated doses [16]. A recent study concluded that the administration of the drug improves the beneWts of dietary Wbre by preventing its bacterial degradation [17].…”