Pharmacokinetics of apomorphine in parkinsonian patients

Nicolle, E.; Pollak, Pierre; Serre-Debeauvais, F; Richard, Ph.; Cl, Gervason; Broussolle, Emmanuel; Gavend, M

doi:10.1111/j.1472-8206.1993.tb00238.x

Cited by 51 publications

(43 citation statements)

References 13 publications

(5 reference statements)

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“…After subcutaneous injection, apomorphine is rapidly absorbed, reaches maximal plasma concentration between 7.8 min [Gancher et al, 1989] and 20 min [Przedborski et al, 1995;Nicolle et al, 1993] and is almost completely cleared after 120 min. As suggested by Przedborski et al [1995], a possible explanation of the difference in Tmax between the different studies may be related to the concentration of the apomorphine solution injected.…”

Section: Discussionmentioning

confidence: 99%

Electroencephalographic Characterization of Brain Dopaminergic Stimulation by Apomorphine in Healthy Volunteers

et al. 1999

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Apomorphine, a dopamine receptor agonist (given in a dose of 0.75 mg s.c.), was administered to 8 healthy volunteers; electroencephalograph (EEG) and event-related potential (ERP) mapping were performed before dosing and 0.5, 1.5 and 2.5 h after dosing. Apomorphine caused an overall increase in beta activity at time 0.5 h in both absolute and relative energy; P300 and CNV ERPs were not significantly altered, although a tendency towards increased P300 latency was seen. The results confirm that the EEG mapping technique is sufficiently sensitive to monitor dopaminergic neurochemical stimulation by means of apomorphine. This could lead to a new, non-invasive and repeatable method for monitoring central neuronal systems which is more convenient to apply repeatedly than for example positron emission tomography techniques. Furthermore, electrophysiological techniques undoubtedly constitute an alternative to classical neuroendocrinological methods, allowing a more direct assessment of central nervous system neurotransmission. Finally, these EEG approaches could lead to better characterization of drugs acting on dopaminergic pathways, such as antipsychotics.

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Section: Discussionmentioning

confidence: 99%

Electroencephalographic Characterization of Brain Dopaminergic Stimulation by Apomorphine in Healthy Volunteers

et al. 1999

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“…32,[35][36][37] However, there is high interindividual variability in T max , C max , and plasma concentrations, leading to different areas-under-thecurves. 36,38 Peripheral pharmacokinetics vary in a linear manner with doses across a range of 2 to 8 mg. 36,39,40 The mean duration of antiparkinsonian action is 45 to 60 minutes. 13 Table 1 shows a comparison of the dopamine receptor selectivity and pharmacokinetics of apomorphine with other orally and subcutaneously administered dopamine receptor agonists.…”

Section: Pharmacokinetics and Pharmacodynamics Of Apomorphinementioning

confidence: 99%

Effective Delivery of Apomorphine in the Management of Parkinson Disease

Bhidayasiri¹,

LeWitt²,

Martin³

et al. 2015

Clinical Neuropharmacology

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The clinical utility of long-term oral levodopa therapy in Parkinson disease (PD) is often limited by the emergence of motor complications. Over time, many patients with PD experience regular and/or unpredictable "off" periods, despite taking optimized oral medication regimens, with a major negative impact on their ability to undertake routine activities of daily living and consequently on their overall quality of life. One established approach for treating patients experiencing off periods and controlling motor fluctuations refractory to conventional oral drug therapy is the subcutaneous administration of the dopaminergic agonist apomorphine. This article outlines how the pharmacokinetic properties of apomorphine underpin its efficacy for the treatment of PD and provides practical guidance for the 3 main approaches in which it is used: subcutaneous intermittent apomorphine injection as a "rescue" therapy for off states, subcutaneous continuous apomorphine infusion for PD patients with intractable motor fluctuations as an alternative to other dopaminergic treatment, and in the apomorphine response (or challenge) test for assessment of dopamine-induced motor response in patients thought to have PD, or in establishing the optimal tolerated dose of apomorphine in patients already known to have PD. Also discussed is the management of potential adverse events with subcutaneous administration of apomorphine, the majority of which are mild and easily managed in practice. The importance of a multidisciplinary PD team in the optimal management of PD patients is now recognized, in particular the role of the specialist PD nurse.

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“…Drug C max and AVC are linearly related to dosages, but show a wide interindividual variabilityl'<" thus requiring individually tailored dosages. Clinically, latency to the motor response is 5 to 15 minutes ; [143][144][145] duration of action ranges between 60 and 90 minutes . Due to the very rapid onset of effect, subcutaneous apomorphine has been proposed to quickly solve severe 'off' periods in patients with complicated and complex 'wearing-off' refractory to levodopa pharmacokinetic optimisation strategies.l 1521 Continuous or intermittent subcutaneous infusions of apomorphine via a portable mini-pump have also been attempted in severely disabled patients, [153] but their clinical use is complicated by practical limitations, development of subcutaneous nodules and psychiatric adverse effects.U>" Among the more practical apomorphine routes of administration under investigation (table V), the intranasal route shows the best pharmacokinetic profile, allowing a rapid (less than 10 minutes) onset of effect, [145][146][147][148] …”

Section: 4 Apomorphinementioning

confidence: 99%

Pharmacokinetic Optimisation in the Treatment of Parkinson's Disease

Contin

Riva

Albani

et al. 1996

Clinical Pharmacokinetics

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The current symptomatic treatment of Parkinson's disease mainly relies on agents which are able to restore dopaminergic transmission in the nigrostriatal pathway, such as the dopamine precursor levodopa or direct agonists of dopamine receptors. Ancillary strategies include the use of anticholinergic and antiglutamatergic agents or inhibitors of cerebral dopamine catabolism, such as monoamine oxidase type B inhibitors. Levodopa is the most widely used and effective drug. Its peculiar pharmacokinetics are characterised by an extensive presystemic metabolism, overcome by the combined use of extracerebral inhibitors of the enzyme aromatic-amino acid decarboxylase and rapid adsorption in the proximal small bowel by a saturable facilitated transport system shared with other large neutral amino acids. Drug transport from plasma to the brain is mediated by the same carriers operating in the intestinal mucosa. The main strategies to assure reproducibility of both drug intestinal absorption and delivery to the brain and clinical effect include standardisation of levodopa administration with respect to meal times and a controlled dietary protein intake. The levodopa plasma half-life is very short, resulting in marked plasma drug concentration fluctuations which are matched, as the disease progresses, with swings in the therapeutic response ('wearing-off' phenomena). 'Wearing-off' phenomena can be also associated, at the more advanced disease stages with a 'negative', both parkinsonism-exacerbating and dyskinetic effect of levodopa at subtherapeutic plasma concentrations. Dyskinesias may be also related to high-levodopa, excessive plasma concentrations. Recognition of the different levodopa toxic response patterns can be difficult on a clinical basis alone, and simultaneous monitoring of levodopa concentration-effect relationships may prove useful to disclose the underlying mechanism and in planning the correct pharmacokinetic management. Controlled-release levodopa formulations have been developed in an attempt to smooth out fluctuations in plasma profiles and matched therapeutic responses. The delayed levodopa absorption and lower plasma concentrations which characterise controlled-release formulations compared with standard forms must be taken into account when prescribing dosage regimens and can be complicating factors in the management of the advanced disease stages. The pharmacokinetic and pharmacodynamic characterisation of the other antiparkinsonian agents is hampered by the lack of sensitive and specific analytical methods to measure their very low plasma drug concentrations and by the difficulty in quantitatively assessing overall moderate drug clinical effects. In clinical practice an optimal dosage schedule is still generally found for each patient on an empirical basis. Future strategies should focus on the search for pharmacological agents with a better kinetic profile, particularly a higher and reproducible bioavailability and a predictable relationship between plasma drug concentration and clinical response. ...

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Pharmacokinetics of apomorphine in parkinsonian patients

Cited by 51 publications

References 13 publications

Electroencephalographic Characterization of Brain Dopaminergic Stimulation by Apomorphine in Healthy Volunteers

Electroencephalographic Characterization of Brain Dopaminergic Stimulation by Apomorphine in Healthy Volunteers

Effective Delivery of Apomorphine in the Management of Parkinson Disease

Pharmacokinetic Optimisation in the Treatment of Parkinson's Disease

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