L-dopa treatment failure: explanation and correction.

Rivera‐Calimlim, Leonor; Dujovne, Carlos A.; Lasagna, Louis; Bianchine, Joseph R.

doi:10.1136/bmj.4.5727.93

Cited by 91 publications

(27 citation statements)

References 4 publications

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“…It is well established, for example, that the absorption of this compound can be reduced or retarded by concomitant food intake (Rivera-Calimlim et al, 1970;.…”

Section: Discussionmentioning

confidence: 99%

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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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“…It is well established, for example, that the absorption of this compound can be reduced or retarded by concomitant food intake (Rivera-Calimlim et al, 1970;.…”

Section: Discussionmentioning

confidence: 99%

“…The stomach has a very limited capacity to absorb levodopa, but can decarboxylate this drug (Rivera-Calimlim et al, 1970). Thus, the major role of the stomach is as a valve, controlling the delivery of an ingested levodopa dose to the intestine absorptive sites (Nutt and Fellman, 1984).…”

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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“…This mechanism would be important for levodopa due to the stomach has a very limited capacity to absorb this drug, but can decarboxylate it (Rivera-Calimlim et al, 1970).…”

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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“…mean) corrected for optimal levodopa dose after 3 months treatment to side effects of levodopa and treatment failure has been reported in which levodopa was not being adequately absorbed (Rivera-Calimlim, Dujovne, Morgan, Lasagna & Bianchine, 1970). Also, anticholinergic drugs reduce gastric motility and might thereby diminish or delay absorption of levodopa.…”

Section: Discussionmentioning

confidence: 99%

The Absorption and Metabolism of a Standard Oral Dose of Levodopa in Patients With Parkinsonism

Bergmann

Curzon

Friedel

et al. 1974

Brit J Clinical Pharma

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1 The metabolism of a standard oral dose of levodopa was studied in forty-two patients with Parkinsonism. Plasma levodopa and 3-o-methyldopa concentrations were estimated at intervals for 8 h after ingestion and the concentration of homovanillic acid (HVA) in the lumbar cerebrospinal fluid (CSF) was measured at 8 hours. Clinical responses 3 months after the test were compared with these findings. 2 Although therapeutic benefit correlated significantly with calculated estimates of both plasma levodopa concentration and CSF HVA at optimal levodopa dose, individual values were widely scattered. There was no significant correlation between toxic effects and plasma levodopa or CSF HVA; and 3-o-methyldopa concentrations similarly did not show a significant correlation with either toxic or therapeutic effects. 3 Blood and CSF levels of levodopa or the metabolites measured in this study were not significantly altered by concurrent treatment with either anticholinergic drugs or amantadine nor by previous treatment with levodopa.

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L-dopa treatment failure: explanation and correction.

Cited by 91 publications

References 4 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

The Absorption and Metabolism of a Standard Oral Dose of Levodopa in Patients With Parkinsonism

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