Hydrosoluble fiber (Plantago ovata husk) and levodopa II: Experimental study of the pharmacokinetic interaction in the presence of carbidopa

Abstract

Levodopa combined with carbidopa constitutes one of the most frequent medication in the treatment of Parkinson's disease. Plantago ovata husk (water-soluble fiber) improves levodopa absorption conditions, but when this drug is administered with carbidopa, fiber could reduce its effectiveness. The purpose of this study is to investigate whether the presence of P. ovata husk modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route with carbidopa (5 mg/ kg). We have also studied whether pharmacokinetic modifications are fiber-dose dependent (100 and 400 mg/kg). When levodopa and carbidopa were administered with 100 mg/kg P. ovata husk, the value of AUC for levodopa diminishes 29.7% (sign, n = 6, P b 0.05) and C max 28.1% (sign, n = 6, P b 0.05) in relation to the values obtained when these drugs were administered without fiber. If the dose of fiber was 400 mg/kg, the decrease was smaller: 20.4% for AUC (no significant difference) and 24.6% for C max (sign, n = 6, P b 0.05), that may indicate an inhibitory action of AADC by the fiber or any of its partial hydrolysis products. On the other hand, since certain time on, levodopa concentrations are always higher in the groups that receive fiber: 210 min with 100 mg/kg and 150 min with 400 mg/kg. The administration of P. ovata husk with levodopa/carbidopa to patients with Parkinson disease could be beneficial and in particular in those patients who also suffer constipation due to an improvement of levodopa kinetic profile with higher final concentrations, a longer plasma half-life and lower C max .

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

“…The AUC values found on day 1 of treatment (112.7, 108.4, 131.2 and 125.5 μg min ml − 1 , respectively, in groups 1, 2, 3 and 4) are similar to those reported by Fernandez et al [12] after administration of a single dose of levodopa/carbidopa and fiber to rabbits (109 and 129 μg min ml − 1 , respectively, with 100 and 400 mg/kg of fiber). The values reported by these authors for C max (1.97 and 2.07 μg ml − 1 , with 100 and 400 mg/kg of fiber, respectively) were also similar to those obtained in this study (2.02, 2.03, 2.00 and 2.04 μg ml − 1 , respectively, in groups 1, 2, 3 and 4).…”

“…In previous studies, we found an improvement in some pharmacokinetic parameters of levodopa when administered with Plantago ovata husk alone or in the presence of carbidopa. We observed higher final concentrations of levodopa, a longer plasma half-life, and lower values of C max [11,12]. However, the AUC values diminished when levodopa/carbidopa were administered with fiber (possibly because fiber retains part of the carbidopa) although there was less of a decrease at higher fiber doses.…”

“…In a previous study [12] in which a single dose of these drugs was given to rabbits, it was demonstrated that the AUC values diminished in the presence of P. ovata husk: 29.7% after the administration of 100 mg/kg fiber, and 20.4% with 400 mg/kg fiber. However, these decreases were larger than those found in the present study.…”

“…However, these decreases were larger than those found in the present study. This previous study also Table 3 Values of C min and C max (μg/ml) obtained after oral administration of 20:5 mg/kg levodopa/carbidopa and Plantago ovata husk (100 or 400 mg/kg) for 7 and 14 days to rabbits 100 mg/kg 400 mg/kg x ± SD CV (%) x ± SD CV (%) had larger decreases in C max with both doses of fiber: 28.1% with 100 mg/kg fiber, and 24.6% with 400 mg/kg [12]. The final plasma concentrations are always higher in the presence of P. ovata husk, with the greatest concentrations occurring after administration of 400 mg/kg fiber.…”

Effects of slowed gastrointestinal motility on levodopa pharmacokinetics

“…In this study, on day 1 of treatment (1.73 μg ml − 1 day 1 of 7, and 1.72 μg ml − 1 day 1 of 14), this parameter was lower than that obtained in a previous study when gastrointestinal motility was not slowed after a single administration of the drugs (2.74 μg ml − 1 , Fernandez et al, 2005) as well as after repeated administration: 2.47 μg ml − 1 day 1 of 7, and 2.55 μg ml − 1 day 1 of 14 (Fernandez et al, in press). On day 7 of treatment, the values of C max in the current work were much lower than in the previous work (normal gastrointestinal motility): 1.99 μg ml − 1 vs 2.70 μg ml − 1 (Fernandez et al, in press).…”