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

Bergmann, S.; Curzon, G.; Friedel, J.; Godwin-Austen, R B; Marsden, C. D.; Parkes, J. D.

doi:10.1111/j.1365-2125.1974.tb00280.x

Cited by 22 publications

(13 citation statements)

References 15 publications

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“…They reported about 50% urinary excretion of these metabolites, which is in good agreement with our value. The plasma levodopa levels and the urinary excretion pattern following oral administration of levodopa in the parkinsonian patients in the present study were similar to previous (18,20,21) results.…”

Section: Discussionsupporting

confidence: 92%

Dosage form Design for Improvement of Bioavailability of Levodopa II: Bioavailability of Marketed Levodopa Preparations in Dogs and Parkinsonian Patients

Sasahara

Nitanai

Habara

et al. 1980

Journal of Pharmaceutical Sciences

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Section: Discussionsupporting

confidence: 92%

Dosage form Design for Improvement of Bioavailability of Levodopa II: Bioavailability of Marketed Levodopa Preparations in Dogs and Parkinsonian Patients

Sasahara

Nitanai

Habara

et al. 1980

Journal of Pharmaceutical Sciences

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“…These findings were attributed to the observation that the activity of ,gut, liver and erythrocyte decarboxylase decreases with long term levodopa administration through an unknown mechanism (Dairman et al 1971;Tanaka et al 1973;Tate et al 1971). However, in another study, no correlation between duration of treatment and plasma levodopa concentrations could be discerned (Bergmann et al 1974). (Table VI) The volume of distribution of levodopa has been estimated to be 0.9 to 1.6 L/kg (Granerus et al 1973;Nutt et al 1985), and plasma clearance 0.5 L/kgfh in the absence of dopa decarboxylase inhibition.…”

Section: Absorption and Distributionmentioning

confidence: 71%

“…In the fasting state, peak plasma concentrations are observed within 1 to 2 hours (Bergmann et al 1974;Evans et al 1980;Rossor et al 1980;Sasahara et al 1980a,b;Wade et al 1974). The latter investigators found that following a single 1000mg dose, peak plasma levodopa concentrations varied lO-fold, from 0.25 to 2.42 mg/L.…”

Section: Absorption and Distributionmentioning

confidence: 93%

Clinical Pharmacokinetics of Anti-Parkinsonian Drugs

Cedarbaum

1987

Clinical Pharmacokinetics

172

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Of the neurological disorders, none can claim a battery of therapeutic agents based upon as rational a pharmacology as can Parkinson's disease. In this review, the clinical pharmacokinetics of the major classes of anti-Parkinsonian drugs is discussed. Although they are the oldest drugs in the anti-Parkinsonian armamentarium, little pharmacokinetic data are available regarding the anticholinergic and antihistaminic agents. Based on elimination half-lives of 10 to 18 hours, most could probably be effectively given on a twice-daily schedule. Amantadine is unique among anti-Parkinsonian agents both in lacking a clearly defined mechanism of action and in being eliminated from the body exclusively by renal excretion of unchanged drug. Thus the normal decline of renal function in the elderly Parkinsonian population becomes an important factor in avoiding potential drug toxicity. The pharmacokinetics and pharmacodynamics of levodopa are complex. Since it is an amino acid, it follows metabolic pathways and must compete for absorption and brain uptake with a number of large neutral amino acids. It has a short elimination half-life and, as Parkinson's disease progresses, the brain loses its capacity to store the drug and becomes dependent in a moment-to-moment fashion on plasma levodopa concentrations, creating therapeutic response fluctuations in over 50% of patients. Pharmacokinetic considerations in the management of these response fluctuations are discussed. The newest class of anti-Parkinsonian agents are the direct acting dopamine receptor agonists. These drugs, all derivatives of ergot, have more prolonged durations of anti-Parkinsonian action than levodopa. However, other than bromocriptine, clinical experience with members of this class of drugs is still limited.

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“…The levodopa plasma concentration vs time profile following oral doses show the erratic behaviour reported elsewhere (Bergmann et al, 1974;Wade et al, 1974;Evans et al, 1981). There was considerable variability both within and between subjects.…”

Section: Oral Datamentioning

confidence: 82%

The pharmacokinetics of intravenous and oral levodopa in patients with Parkinson's disease who exhibit on‐off fluctuations.

Hardie¹,

Malcolm²,

Lees³

et al. 1986

Brit J Clinical Pharma

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We have studied the clinical effects and pharmacokinetics of levodopa infusions and oral therapy in seven patients with Parkinson's disease. They all showed on‐off fluctuations whilst receiving long‐term treatment with levodopa in combination with a peripheral decarboxylase inhibitor. Intravenous infusion at a constant rate for up to 16 h resulted in a smoother clinical response, and maintained plasma levodopa concentrations within narrower limits compared with conventional oral therapy. Following infusion rates of 32‐80 mg h‐1 (0.5‐1.3 mg kg‐1 h‐1) the plasma concentration associated with optimum therapeutic response lay between 0.3 and 1.6 mg l‐1. There was considerable variation in the oral absorption and elimination of levodopa, both within and between subjects. The concentration of 3‐OMe dopa in plasma hardly increased during each day's levodopa therapy. In all cases levels were greater than the maximum concentrations of levodopa, sometimes by as much as a factor of 10. In contrast to most previous reports on the pharmacokinetics of levodopa, the data presented here are consistent with a two‐compartment kinetic model. It is not known whether the difference in pharmacokinetics is due to chronic therapy or whether it is specific to those patients who show on‐ off phenomena, but such changes might be related in some way to the development of fluctuations in clinical response.

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

Cited by 22 publications

References 15 publications

Dosage form Design for Improvement of Bioavailability of Levodopa II: Bioavailability of Marketed Levodopa Preparations in Dogs and Parkinsonian Patients

Dosage form Design for Improvement of Bioavailability of Levodopa II: Bioavailability of Marketed Levodopa Preparations in Dogs and Parkinsonian Patients

Clinical Pharmacokinetics of Anti-Parkinsonian Drugs

The pharmacokinetics of intravenous and oral levodopa in patients with Parkinson's disease who exhibit on‐off fluctuations.

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