Dosage form design for improvement of bioavailability of levodopa III: Influence of dose on pharmacokinetic behavior of levodopa in dogs and parkinsonian patients

Sasahara, Kunihiro; Nitanai, Takashi; Habara, Taeko; Morioka, Tadashi; Nakajima, Eiichi

doi:10.1002/jps.2600691205

Cited by 33 publications

(18 citation statements)

References 7 publications

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“…For ipratropium, passive diffusion across the membrane was highly overestimated, while for lisinopril carrier-mediated transport was over predicted. For levodopa the model predicted decreasing uptake efficiencies for the reported doses (E = 44-17%) which was not observed experimentally (E ≈ 86%) (Zhao et al, 2001;Robertson et al, 1989;Sasahara et al, 1980).…”

Section: Pharmaceuticalscontrasting

confidence: 49%

Including carrier-mediated transport in oral uptake prediction of nutrients and pharmaceuticals in humans

O’Connor

Veltman

Huijbregts

et al. 2014

Environmental Toxicology and Pharmacology

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Section: Pharmaceuticalscontrasting

confidence: 49%

Including carrier-mediated transport in oral uptake prediction of nutrients and pharmaceuticals in humans

O’Connor

Veltman

Huijbregts

et al. 2014

Environmental Toxicology and Pharmacology

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“…With long term administration levodopa absorption appears to become more efficient and complete (Muenter & Tyce 1971;Rivera-Calimlim 1972). This may be due to either saturation of tissue storage sites (Rivera-Calimlim 1972), resulting in less trapping of transported drug; alterations in the carrier itself; saturation of gut wall decarboxylase (Sasahara et al 1980b) or perhaps its inhibition by a metabolic product of dopa such as 3-O-methyldopa accumulated in the tissue. It is also possible that at higher doses a second, lowaffinity, non-saturable uptake mechanism becomes active.…”

Section: Absorption and Distributionmentioning

confidence: 94%

“…Intrapatient variability in plasma levodopa concentrations is less than interpatient variability Wade et al 1974). In patients given incremental doses, the AUC for levodopa increased proportionally to the dose in mg/kg (Sasahara et al 1980b). However, the ratio oflevodopa to circulating dopamine decreased, suggesting that with increasing doses, a decreasing proportion of each dose is decarboxylated in the gut.…”

Section: Absorption and Distributionmentioning

confidence: 97%

“…(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. In studies employing orally administered levodopa only, the decline in plasma concentrations appeared to be monophasic, with a mean apparent elimination half-life ranging from 0.78 hours (Sasahara et al 1980b) to I. 74 hours (Rossor et al 1980).…”

Section: Absorption and Distributionmentioning

confidence: 97%

See 1 more Smart Citation

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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“…Response parameters other routes (Sasahara et al, 1980a;Poewe, 1993;Muhlack et al, 2004;LeWitt et al, 2009), and several studies report the bioavailability of oral doses relative to IV administration (Sasahara et al, 1980b;Robertson et al, 1989;Kompoliti et al, 2002). The pharmacodynamic data (see Table 3: Reports of Human Experience with IV Levodopa) represent a total of 2760 human subjects, with a significant variety of patient groups and a multitude of response parameters (see Table 1).…”

Section: Patient Populationsmentioning

confidence: 99%