Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease

Mouradian, M. Maral; Heuser, Isabella; Baronti, F.; Chase, Thomas N.

doi:10.1002/ana.410270105

Cited by 221 publications

(100 citation statements)

References 30 publications

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“…Several authors have indicated that the induction of on/off phenomena and dyskinesias may be the result of an active process of adaptation to variations in brain and plasma levodopa levels. In this way, when levodopa concentrations are maintained at a constant level by intravenous infusion dyskinesias and fluctuations are greatly reduced (Mouradian et al, 1990;Chase et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

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

Fernández

Carriedo

Sierra

et al. 2005

European Neuropsychopharmacology

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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 .

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Section: Discussionmentioning

confidence: 99%

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

Fernández

Carriedo

Sierra

et al. 2005

European Neuropsychopharmacology

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Section: Discussionmentioning

confidence: 99%

Hydrosoluble fiber (Plantago ovata husk) and levodopa I: Experimental study of the pharmacokinetic interaction

García¹,

Fernández²,

Carriedo³

et al. 2005

European Neuropsychopharmacology

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Fiber therapy could be used in patients with Parkinson disease to reduce the symptoms of gastrointestinal disorders; however, it could interact with levodopa reducing its effectiveness. In this experimental study we have investigated whether the presence of Plantago ovata husk (water-soluble fiber) modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route at the same time. We have also studied whether pharmacokinetic modifications are fiber-dose dependent (100 and 400 mg/kg). The extent of levodopa absorbed when administering 100 mg/kg of fiber (AUC = 43.4 Ag min ml À 1 ) is approximately the same as when levodopa is administered alone (AUC = 47.1 Ag min ml À 1 ); however, C max is lower (1.04 versus 1.43 Ag ml À 1 ). Results obtained indicate that fiber at the higher dose increases the extent of levodopa absorbed (AUC = 62.2 Ag min ml À 1 ), being the value of C max similar (1.46 Ag ml À 1 ). The value of t max increases from 10 min when levodopa is administered alone to 20 min when the animals receive fiber. On the other hand, since certain time on, levodopa concentrations are always higher in the groups that receive fiber: 60 min with 100 mg/kg fiber and 20 min with 400 mg/kg fiber. Fiber also increases the mean residence time (MRT). P. ovata husk administration with levodopa could be beneficial, not only in patients with constipation, due to: lower adverse reactions (lower values of C max ) and longer and more stable effects (higher final concentrations and more time in the body). D

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“…In addition, these motor response fluctuations can be improved by bypassing the stomach via a non-oral administrative route, such as delivering levodopa directly into the small intestine or intravenously (Mouradian et al, 1990;Nyholm et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Effects of slowed gastrointestinal motility on levodopa pharmacokinetics

Fernández

García

Diez

et al. 2010

Autonomic Neuroscience

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Autonomic disorders are often seen in Parkinson's disease, with disturbances of the gastrointestinal tract occurring most frequently. These disorders, mainly a delay in gastric emptying and slowed gastrointestinal motility, can modify the pharmacokinetics and effectiveness of drugs used to treat Parkinson's disease and administered orally. In this study, we evaluated in a rabbit model the pharmacokinetics of levodopa (administered with carbidopa) in the context of gastrointestinal motility slowed by the administration of an anticholinergic drug. Levodopa + carbidopa (20:5 mg/kg) and the anticholinergic biperiden (100 μg/kg) were orally administered to rabbits over one of two time periods (7 or 14 days) to verify the stabilization of levodopa concentrations. The values of the area under the curve (AUC) and C max were higher on the final day of treatment with an increase in AUC of 25% on day 7 and 33.4% on day 14; for C max , the increase was 15% on day 7 and 12.8% on day 14. The values of AUC and C max were lower than those obtained when levodopa was administered to rabbits with normal gastrointestinal motility. The values obtained for C min (baseline sample obtained before administration) also increased with treatment duration (24% and 47.4% on days 7 and 14, respectively). These values were higher than those obtained in the absence of anticholinergic administration. We conclude that, under our experimental conditions of slowed gastrointestinal motility, levodopa absorption diminishes, and final concentrations and C min are higher than under conditions of normal motility.

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Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease

Cited by 221 publications

References 30 publications

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

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

Hydrosoluble fiber (Plantago ovata husk) and levodopa I: Experimental study of the pharmacokinetic interaction

Effects of slowed gastrointestinal motility on levodopa pharmacokinetics

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