Pharmacokinetics of a Once-Daily extended-release formulation of pramipexole in healthy male volunteers: Three studies

Jenner, Peter; Könen-Bergmann, Michael; Schepers, Cornelia; Haertter, Sebastian

doi:10.1016/j.clinthera.2009.10.018

Cited by 51 publications

(39 citation statements)

References 24 publications

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“…Once-daily, oral extended-release formulations are now available for ropinirole and pramipexole. [19,20] The rotigotine transdermal patch [21] is available for use in all stages of Parkinson's disease in Europe, and for early-stage Parkinson's disease in the US (although the US FDA suspended the marketing authorization in 2008 [22] ).…”

Section: Pharmacokineticsmentioning

confidence: 99%

Dopamine Receptor Agonists for the Treatment of Early or Advanced Parkinsonʼs Disease

2010

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Dopamine receptor agonists are indicated for the symptomatic treatment of early, moderate or advanced Parkinson's disease as well as for the reduction of levodopa-related motor complications. Ergolinic dopamine agonists, such as bromocriptine or pergolide, were initially developed and marketed, and then non-ergolinic dopamine agonists, such as pramipexole and ropinirole, were introduced, reducing the risk of drug-induced fibrotic reactions. Once-daily, controlled-release oral and transdermal formulations have been developed aiming at providing more stable 24-hour plasma drug concentrations and more convenient administration. A disease-modifying effect of dopamine agonists has not been demonstrated clinically. As with any other drug, dopamine agonists can also cause adverse drug reactions, which can be related or unrelated to dopaminergic hyperactivation. Dopaminergic reactions include nausea, hallucinations, confusion and orthostatic hypotension, among others, which were readily identified in pre-marketing clinical trials. During post-marketing surveillance, important adverse reactions were identified, such as daytime somnolence, impulse-control disorders and heart valve fibrosis. Other issues, including the efficacy of dopamine agonists for the treatment of non-motor symptoms, remain under evaluation.

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Section: Pharmacokineticsmentioning

confidence: 99%

Dopamine Receptor Agonists for the Treatment of Early or Advanced Parkinsonʼs Disease

2010

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“…Sustained-release (SR) formulations of PPX, the same formulation with extended-release PPX, showed similar pharmacokinetics and tolerability as equivalent dose IR PPX 8,9. In clinical trials, PPX SR has demonstrated similar therapeutic efficacy and safety profile as PPX IR, both in early and advanced PD 9–16.…”

Section: Introductionmentioning

confidence: 99%

Analysis of pramipexole dose–response relationships in Parkinson's disease

Wang

Sun

Zhu

et al. 2016

DDDT

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BackgroundPramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson’s disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined.MethodsChinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson’s Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment.ResultsSustained-release (SR) and immediate-release (IR) PPX showed similar efficacy based on score changes at 18 weeks, with comparable tolerability. Approximately two-third of patients received PPX at ≥1.5 mg/d, and one fourth of patients had ≥20% tremor contribution to UPDRS II+III. After treatment, patients receiving PPX ≥1.5 mg/d showed better improvement in UPDRS II+III scores (P=0.0025), with similar trends with the IR and SR formulations. Patients with ≥20% tremor contribution showed better improvement in UPDRS II+III scores (P=0.0017). No differences were seen based on PD stage or combined levodopa dose. The overall proportions of adverse events (AEs) were similar. More patients discontinued because of intolerable side effects, and more investigator-defined drug-related AEs were recorded in the <1.5 mg/d subgroup.ConclusionUPDRS II+III improvement was better with PPX ≥1.5 than with <1.5 mg/d in Chinese PD patients after 18 weeks of treatment, with similar trends seen with IR and SR formulations. The frequency of AEs in PPX ≥1.5 and <1.5 mg/d subgroups was similar.

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“…Moreover, compared with three-times daily administration of a standard non-ergolinic DA, once-daily administration of a long-acting non-ergolinic DA results in less fluctuating plasma concentrations over 24 h; this greater consistency in drug delivery could, in turn, result in a more continuous therapeutic effect (i.e. dopaminergic stimulation) [29,42], although this remains to be proven (see Sect. 1).…”

Section: Place Of Pramipexole Extended-release In the Management Of Pmentioning

confidence: 98%

“…In healthy volunteers, pramipexole ER 4.5 mg administered once daily was bioequivalent to pramipexole IR 1.5 mg administered three times daily with respect to the area under the plasma concentration-time curve from time zero to 24 h (AUC 24 ) and the maximum plasma concentration (C max ) [8,10,29]. Coadministration of pramipexole ER with food (high-fat meal) did not affect AUC 24 , nor did it increase C max to a clinically meaningful extent [8,10,29]. Drug interactions with pramipexole are considered unlikely, based upon its low plasma protein binding and minimal metabolism [8,10,13] (Table 2).…”

Section: Pharmacological Propertiesmentioning

confidence: 99%

Pramipexole Extended-Release: A Review of Its Use in Patients with Parkinson’s Disease

Frampton

2014

Drugs

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Pramipexole, a non-ergolinic, D3-preferring dopamine agonist (DA), is well established as a treatment option for motor symptoms at all stages of Parkinson's disease (PD). It is administered orally and is available as both a three-times daily immediate-release (IR) formulation and a once-daily extended-release (ER) formulation (Mirapex(®) ER, Mirapexin(®) ER; Pexola(®) ER, Sifrol(®) ER). The two formulations are bioequivalent; the majority (>80 %) of patients can be switched overnight from pramipexole IR to ER without the need for dosage adjustment. In terms of improving activities of daily living and motor function in short-term (≤33-week), double-blind studies, pramipexole ER was noninferior to pramipexole IR and significantly more effective than placebo as monotherapy in patients with early PD, and similar to pramipexole IR and significantly more effective than placebo as adjunctive therapy to levodopa in patients with advanced PD. In long-term (80-week) extensions of these trials, open-label treatment with pramipexole ER was associated with sustained symptomatic benefit. Moreover, the majority of extension participants who responded to a simple convenience questionnaire expressed a preference for once-daily over three-times daily dosing. Pramipexole ER was generally well tolerated in clinical trials; no new or unexpected safety signals were identified compared with the IR formulation. Head-to-head trials are needed in order to fully define the role of pramipexole ER relative to other once-daily formulations of DAs (oral ropinirole and transdermal rotigotine). Nonetheless, by reducing the pill burden, the ER formulation of pramipexole provides a more convenient alternative to the IR formulation; studies specifically testing whether this translates into improved patient compliance and symptom control are worthwhile.

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Pharmacokinetics of a Once-Daily extended-release formulation of pramipexole in healthy male volunteers: Three studies

Cited by 51 publications

References 24 publications

Dopamine Receptor Agonists for the Treatment of Early or Advanced Parkinsonʼs Disease

Dopamine Receptor Agonists for the Treatment of Early or Advanced Parkinsonʼs Disease

Analysis of pramipexole dose–response relationships in Parkinson's disease

Pramipexole Extended-Release: A Review of Its Use in Patients with Parkinson’s Disease

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Pharmacokinetics of a Once-Daily extended-release formulation of pramipexole in healthy male volunteers: Three studies

Cited by 51 publications

References 24 publications

Dopamine Receptor Agonists for the Treatment of Early or Advanced Parkinsonʼs Disease

Dopamine Receptor Agonists for the Treatment of Early or Advanced Parkinsonʼs Disease

Analysis of pramipexole dose&ndash;response relationships in Parkinson&#39;s disease

Pramipexole Extended-Release: A Review of Its Use in Patients with Parkinson’s Disease

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Analysis of pramipexole dose–response relationships in Parkinson's disease