Intranasal Apomorphine in Parkinsonian On-Off Fluctuations

Laar, Teus van; Jansen, E. N. H.; Essink, A.W.G.; Neef, Cees

doi:10.1001/archneur.1992.00530290064013

Cited by 48 publications

(18 citation statements)

References 11 publications

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“…The results of this study confirm the usefulness of the intranasal route to administer apomorphine as suggested by Kapoor et al and Laar et al (8,9) in their clinical studies. One should, however, take into account a relatively poor and variable bioavailability.…”

Section: Resultssupporting

confidence: 90%

“…Assuming that, the subcutaneous dose penetrates quantitatively into the blood stream (6), the mean bioavailability of the intranasal dose was 45.0 ± 15% (n = 6). The estimated bioavailability of 90-100% of the intranasal dose compared to a subcutaneous dose, observed in one patient by Laar et al (9), seems therefore to be purely incidental.…”

Section: Plasma Level Time Profiles and Pharmacokinetic Parametersmentioning

confidence: 83%

“…Therefore, development of more convenient dosage forms could lead to improved compliance, less costly regimen and improved quality of life of patients suffering from Parkinsonism. Some recent reports suggest that intranasal administration is as effective as subcutaneous injections, with regard to duration of action and quality of motor response (8,9). However, comparative pharmacokinetic data on the two routes are not yet available.…”

Section: Introductionmentioning

confidence: 99%

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Apomorphine pharmacokinetics in Parkinsonism after intranasal and subcutaneous application

Sam

Jeanjean

Maloteaux

et al. 1995

Eur. J. Drug Metab. Pharmacokinet.

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Apomorphine was administered subcutaneously and intranasally to 7 patients suffering from Parkinsonism with 'on-off' problems. This comparative pharmacokinetic study showed that the two routes of administration are comparable with respect to absorption kinetics. Apomorphine is rapidly absorbed when administered intranasally or subcutaneously with an absorption half life of 8.6 min and 5.8 min, respectively. The high rate of absorption is also reflected by the time for the plasma concentration to peak (tmax) and the lag times. The tmax was 23 min for intranasal route and 18 min for the subcutaneous route while the lag times were 2.8 min and 3.9 min, respectively. The bioavailability of intranasal apomorphine compared to the subcutaneous route amounted to 45%. After intranasal and subcutaneous administrations, the elimination half life of apomorphine amounted to 31 min and 27 min, respectively.

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Section: Resultssupporting

confidence: 90%

Section: Plasma Level Time Profiles and Pharmacokinetic Parametersmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Apomorphine pharmacokinetics in Parkinsonism after intranasal and subcutaneous application

Sam

Jeanjean

Maloteaux

et al. 1995

Eur. J. Drug Metab. Pharmacokinet.

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“…Thus, ongoing basic research (e.g., Carey et al, 1995) is aimed to improve the applicability of L-DOPA treatment, by trying to further the understanding of the drug's mechanisms of action and by improving its pharmacokinetics. Here, intranasal drug administration might provide an interesting route, especially since the DA agonist apomorphine was found to be effective by this route in the treatment of Parkinson's disease (Kapoor et al, 1990;van Laar et al, 1992). With respect to L-DOPA, we recently found that intranasal administration of L-DOPA methyl ester (without peripheral AADC inhibition) in the rat can increase extracellular DA levels in the neostriatum (de Souza Silva et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Increased neostriatal dopamine activity after intraperitoneal or intranasal administration of L-DOPA: On the role of benserazide pretreatment

Silva

Mattern

Hacker

et al. 1997

Synapse

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L-DOPA provides the most potent medication to treat Parkinson's disease, and such systemic treatment is usually combined with a peripheral amino acid decarboxylase inhibitor to amplify its central effectiveness. Since L-DOPA can lose its efficacy or can lead to adverse effects with prolonged application, current pharmacokinetic and dynamic research is aimed at improving the drug's applicability. In a previous study, performed with in vivo microdialysis in the anesthetized rat, we have shown that intranasal L-DOPA administration (without prior decarboxylase inhibition) can increase extracellular dopamine levels in the neostriatum. Using similar experimental conditions in the present experiment, we tested the neurochemical effects of L-DOPA treatment in combination with the peripheral amino acid decarboxylase inhibitor benserazide. In accordance with other data, it was found that the combination of i.p. benserazide and i.p. L-DOPA led to pronounced increases of extracellular levels of dopamine, dihydroxyplenylacetic acid and homovanillic acid in the neostriatum, whereas i.p. L-DOPA alone only moderately increased dopamine, but strongly increased the metabolite levels. Furthermore, increased dopamine levels, and weaker increases of dihydroxyplenylacetic acid and homovanillic acid were observed after i.p. benserazide followed by intranasal L-DOPA. Finally, we found that i.p. benserazide alone can lead to pronounced increases in neostriatal dopamine and moderate increases of dihydroxyplenylacetic acid levels, whereas it did not affect homovanillic acid. Thus, not only the combination of L-DOPA (i.p. or intranasal) with the presumed peripheral L-DOPA decarboxylase inhibitor benserazide, but also each component alone can affect dopamine activity in the brain. Especially the findings with benserazide treatment might be of relevance for understanding the mechanisms of current L-DOPA therapy, since they indicate that part of the treatment's actions may possibly be determined by central dopaminergic effects of the accompanying amino acid decarboxylase inhibitor.

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“…Apomorphine is well absorbed after nasal administration of an aqueous solution. The time of onset and duration of action are equivalent to the subcutaneous injection (Van Laar et al 1992). However, administration of an intranasal solution faces several problems such as drainage from the site of application and irregular deposition within the nasal cavity.…”

Section: Case Study -Apomorphine In Situ Gelmentioning

confidence: 99%

Design of Experiments: Basic Concepts and Its Application in Pharmaceutical Product Development

Patravale¹,

Disouza²,

Rustomjee³

2016

Pharmaceutical Product Development

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Intranasal Apomorphine in Parkinsonian On-Off Fluctuations

Cited by 48 publications

References 11 publications

Apomorphine pharmacokinetics in Parkinsonism after intranasal and subcutaneous application

Apomorphine pharmacokinetics in Parkinsonism after intranasal and subcutaneous application

Increased neostriatal dopamine activity after intraperitoneal or intranasal administration of L-DOPA: On the role of benserazide pretreatment

Design of Experiments: Basic Concepts and Its Application in Pharmaceutical Product Development

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