The effect of an increased ratio of carbidopa to levodopa on the pharmacokinetics of levodopa

Kaakkola, Seppo; Männistö, Pekka T.; Nissinen, Erkki; Vuorela, Annamari; Mäntylä, R

doi:10.1111/j.1600-0404.1985.tb00888.x

Cited by 31 publications

(13 citation statements)

References 21 publications

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“…After the administration of 100 mg levodopa combined with a dopa decarboxylase inhibitor, the values obtained for C max were next to 1000 ng/ml [16–18]. In our study, in the initial situation of patients, the data ranged from 343.1 to 1433.9 ng/ml, so, in some patients the values were similar to that found by other authors and in others it was lower.…”

Section: Discussionsupporting

confidence: 88%

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A randomised clinical trial to evaluate the effects of Plantago ovata husk in Parkinson patients: changes in levodopa pharmacokinetics and biochemical parameters

Fernández

Hernandez-Echevarria

Sierra

et al. 2014

BMC Complement Altern Med

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BackgroundPlantago ovata husk therapy could be used in patients with Parkinson disease to reduce the symptoms of gastrointestinal disorders, but it is important to know whether this compound modifies levodopa pharmacokinetics. The maintenance of constant plasma concentrations of levodopa abolishes the clinical fluctuations in parkinsonian patients. The aim of this randomised clinical trial was to establish the influence of the fiber Plantago ovata husk in the pharmacokinetics of levodopa when administered to Parkinson patients well controlled by their oral medication.MethodsTo evaluate the effects of this fiber on several biochemical parameters. 18 volunteers participated in the study and received alternatively two treatments (Plantago ovata husk or placebo) with their usual levodopa/carbidopa oral dose. On days 0 (initial situation), 14 and 35 of the study, blood samples were taken to assess levodopa pharmacokinetics and to determine biochemical parameters.ResultsLevodopa Cmax was very similar in the initial situation (603.2 ng/ml) and after placebo administration (612.0 ng/ml), being slightly lower (547.8 ng/ml) when Plantago ovata husk was given. AUC was very similar in the three groups: initial situation.- 62.87 μg.min/ml, fiber treatment.- 64.47 μg.min/ml and placebo treatment.- 65.10 μg.min/ml. Fiber reduced significantly the number of peaks observed in the levodopa concentrations, maintaining concentrations more stable. No significant differences were found in total cholesterol, LDL-cholesterol and triglycerides with the administration of Plantago ovata husk.ConclusionsPlantago ovata husk administration caused a smoothing and homogenization of levodopa absorption, providing more stable concentrations and final higher levels, resulting in a great benefit for patients.Trial registrationEudraCT2006-000491-33

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Section: Discussionsupporting

confidence: 88%

“…This parameter ranged from 20 to 90 minutes as in other studies [10, 17, 19]. However, the mean AUC value (62.87 μg.min/ml) was slightly lower than that found by other authors using the same dose of levodopa: 98.9 μg.min/ml [16], 99.7 μg.min/ml [18], 117.0 μg.min/ml [17]. …”

Section: Discussionmentioning

confidence: 50%

A randomised clinical trial to evaluate the effects of Plantago ovata husk in Parkinson patients: changes in levodopa pharmacokinetics and biochemical parameters

Fernández

Hernandez-Echevarria

Sierra

et al. 2014

BMC Complement Altern Med

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“…Smucker’s, Orrville, OH, USA), while they were housed singly for 30–60 min (depending on how readily they ingested the mixture). Carbidopa inhibits peripheral metabolism of levodopa which indirectly allows for penetration of levodopa across the blood brain barrier for a central nervous system effect [52,53]. The percent ingested was recorded to ensure that at least 90% of the mixture was ingested by each rat.…”

Section: Methodsmentioning

confidence: 99%

Vocal training, levodopa, and environment effects on ultrasonic vocalizations in a rat neurotoxin model of Parkinson disease

Kelm‐Nelson

Bräuer

Ciucci

2016

Behavioural Brain Research

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Levodopa does not improve dysarthria in patients with Parkinson Disease (PD), although vocal exercise therapy, such as “LSVT/LOUD®”, does improve vocal communication. Most patients receive vocal exercise therapy while concurrently being treated with levodopa, although the interaction between levodopa and vocal exercise therapy on communication in PD is relatively unknown. Further, carryover of vocal exercise therapy to novel situations is critical for successful outcomes, but the influence of novel situations on rehabilitated vocal communication is not well understood. To address the influence of exercise, medications, and environment on vocal communication with precise experimental control, we employed the widely used 6-OHDA rat neurotoxin model of PD (infusion to the medial forebrain bundle), and assessed ultrasonic vocalizations after: vocal exercise, vocal exercise with levodopa, levodopa alone, and control conditions. We tested USVs in the familiar training environment of the home cage and a novel cage. We hypothesized that parkinsonian rats that undergo vocal exercise would demonstrate significant improvement of ultrasonic vocalization (USV) acoustic parameters as compared to the control exercise and levodopa-only treatment groups. We further hypothesized that vocal exercise in combination with levodopa administration, similar to what is common in humans, would lead to improvement in USV outcomes, particularly when tested in a familiar versus a novel environment. We found that the combination of exercise and levodopa lead to some improvement in USV acoustic parameters and these effects were stronger in a familiar vs. a novel environment. Our results suggest that although treatment can improve aspects of communication, environment can influence the benefits of these effects.

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“…By doing so, they permit reduction of total daily levodopa dosage (Cedarbaum 1987). They also reduce levodopa side effects arising from peripheral dopamine-receptor stimulation (e.g., nausea and vomiting) (Kaakkola et al 1985; Markham et al 1974). Pharmacokinetically, they increase the peak plasma levodopa concentration ( C max ), increase overall levodopa exposure [area under the concentration–time curve (AUC)], and prolong levodopa plasma half-life (Cedarbaum 1987; Robertson et al 1989).…”

Section: The Evolution Of Cdd Strategiesmentioning

confidence: 99%

Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery?

2013

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The complications of long-term levodopa therapy for Parkinson’s disease (PD) include motor fluctuations, dyskinesias, and also nonmotor fluctuations—at least equally common, but less well appreciated—in autonomic, cognitive/psychiatric, and sensory symptoms. In seeking the pathophysiologic mechanisms, the leading hypothesis is that in the parkinsonian brain, intermittent, nonphysiological stimulation of striatal dopamine receptors destabilizes an already unstable system. Accordingly, a major goal of PD treatment in recent years has been the attainment of continuous dopaminergic stimulation (CDS)—or, less theoretically (and more clinically verifiable), continuous drug delivery (CDD). Improvements in the steadiness of the plasma profiles of various dopaminergic therapies may be a signal of progress. However, improvements in plasma profile do not necessarily translate into CDS, or even into CDD to the brain. Still, it is reassuring that clinical studies of approaches to CDD have generally been positive. Head-to-head comparative trials have often failed to uncover evidence favoring such approaches over an intermittent therapy. Nevertheless, the findings among recipients of subcutaneous apomorphine infusion or intrajejunal levodopa/carbidopa intestinal gel suggest that nonmotor PD symptoms or complications may improve in tandem with motor improvement. In vivo receptor binding studies may help to determine the degree of CDS that a dopaminergic therapy can confer. This may be a necessary first step toward establishing whether CDS is, in fact, an important determinant of clinical efficacy. Certainly, the complexities of optimal PD management, and the rationale for an underlying strategy such as CDS or CDD, have not yet been thoroughly elucidated.

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The effect of an increased ratio of carbidopa to levodopa on the pharmacokinetics of levodopa

Cited by 31 publications

References 21 publications

A randomised clinical trial to evaluate the effects of Plantago ovata husk in Parkinson patients: changes in levodopa pharmacokinetics and biochemical parameters

A randomised clinical trial to evaluate the effects of Plantago ovata husk in Parkinson patients: changes in levodopa pharmacokinetics and biochemical parameters

Vocal training, levodopa, and environment effects on ultrasonic vocalizations in a rat neurotoxin model of Parkinson disease

Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery?

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