Clinical pharmacokinetics of pramipexole, ropinirole and rotigotine in patients with Parkinson's disease

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Abstract

Introduction: Pramipexole (PRA), ropinirole (ROP) and rotigotine (ROT) are non-ergoline dopaminergic agonists (DAs) used to treat Parkinson's disease (PD). Clinical pharmacokinetics of DAs is poorly characterized in PD. The main purpose of our study was to investigate the effect of dose, age and sex on steady-state plasma concentrations of DAs in real life PD patients on chronic DAs therapy. Methods: The study was single center, open and prospective. Blood samples for measurement of DAs plasma concentrations were drawn in the morning, at a median 18-h distance from the last DA dose. Results: Ninety-one patients treated with PRA, 50 with ROP and 37 with ROT were enrolled in the study. Plasma concentration of DAs significantly correlated with weight-adjusted daily dose in all subgroups, although at a given dose, matched plasma concentrations highly varied among patients. Median PRA plasma concentration-to-daily dose ratio (C/D) [(ng/mL)/(mg/kg/d)] was 68% higher in patients >65 years than ≤65 years (158 vs 94, p < 0.001), while was not affected by age in ROP and ROT subgroups. No sex-mediated differences in C/D ratios were observed in any group. Conclusion: These are the first observations on DAs pharmacokinetics in PD patients’ everyday clinical practice. Of relevance, patients over 65yrs may require about one third of PRA dose compared to under 65yrs to achieve the same plasma concentration. Due to the high intersubject variability in plasma concentrations at the same dosage, we speculate that monitoring of plasma DAs might be helpful in the individualization of treatment in selected patients.

Original languageEnglish
Pages (from-to)111-117
Number of pages7
JournalParkinsonism and Related Disorders
Volume61
DOIs
Publication statusPublished - Apr 1 2019

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Dopamine Agonists
Parkinson Disease
Pharmacokinetics
pramipexole
ropinirole
N 0437
Sex Characteristics
Weights and Measures
Therapeutics

Keywords

  • Clinical pharmacokinetics
  • Dopaminergic agonists
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

@article{19d03f7d7d574951a79848e22e3c0a1e,
title = "Clinical pharmacokinetics of pramipexole, ropinirole and rotigotine in patients with Parkinson's disease",
abstract = "Introduction: Pramipexole (PRA), ropinirole (ROP) and rotigotine (ROT) are non-ergoline dopaminergic agonists (DAs) used to treat Parkinson's disease (PD). Clinical pharmacokinetics of DAs is poorly characterized in PD. The main purpose of our study was to investigate the effect of dose, age and sex on steady-state plasma concentrations of DAs in real life PD patients on chronic DAs therapy. Methods: The study was single center, open and prospective. Blood samples for measurement of DAs plasma concentrations were drawn in the morning, at a median 18-h distance from the last DA dose. Results: Ninety-one patients treated with PRA, 50 with ROP and 37 with ROT were enrolled in the study. Plasma concentration of DAs significantly correlated with weight-adjusted daily dose in all subgroups, although at a given dose, matched plasma concentrations highly varied among patients. Median PRA plasma concentration-to-daily dose ratio (C/D) [(ng/mL)/(mg/kg/d)] was 68{\%} higher in patients >65 years than ≤65 years (158 vs 94, p < 0.001), while was not affected by age in ROP and ROT subgroups. No sex-mediated differences in C/D ratios were observed in any group. Conclusion: These are the first observations on DAs pharmacokinetics in PD patients’ everyday clinical practice. Of relevance, patients over 65yrs may require about one third of PRA dose compared to under 65yrs to achieve the same plasma concentration. Due to the high intersubject variability in plasma concentrations at the same dosage, we speculate that monitoring of plasma DAs might be helpful in the individualization of treatment in selected patients.",
keywords = "Clinical pharmacokinetics, Dopaminergic agonists, Parkinson's disease",
author = "Manuela Contin and Giovanna Lopane and Susan Mohamed and Giovanna Calandra-Buonaura and Sabina Capellari and {De Massis}, Patrizia and Stefania Nassetti and Alessandro Perrone and Roberto Riva and Luisa Sambati and Cesa Scaglione and Pietro Cortelli",
note = "Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Universit{\`a} di Bologna (Contin Manuela, Calandra-Buonaura Giovanna, Capellari Sabina, Riva Roberto, Sambati Luisa, Cortelli Pietro)",
year = "2019",
month = "4",
day = "1",
doi = "10.1016/j.parkreldis.2018.11.007",
language = "English",
volume = "61",
pages = "111--117",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",

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TY - JOUR

T1 - Clinical pharmacokinetics of pramipexole, ropinirole and rotigotine in patients with Parkinson's disease

AU - Contin, Manuela

AU - Lopane, Giovanna

AU - Mohamed, Susan

AU - Calandra-Buonaura, Giovanna

AU - Capellari, Sabina

AU - De Massis, Patrizia

AU - Nassetti, Stefania

AU - Perrone, Alessandro

AU - Riva, Roberto

AU - Sambati, Luisa

AU - Scaglione, Cesa

AU - Cortelli, Pietro

N1 - Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Contin Manuela, Calandra-Buonaura Giovanna, Capellari Sabina, Riva Roberto, Sambati Luisa, Cortelli Pietro)

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Introduction: Pramipexole (PRA), ropinirole (ROP) and rotigotine (ROT) are non-ergoline dopaminergic agonists (DAs) used to treat Parkinson's disease (PD). Clinical pharmacokinetics of DAs is poorly characterized in PD. The main purpose of our study was to investigate the effect of dose, age and sex on steady-state plasma concentrations of DAs in real life PD patients on chronic DAs therapy. Methods: The study was single center, open and prospective. Blood samples for measurement of DAs plasma concentrations were drawn in the morning, at a median 18-h distance from the last DA dose. Results: Ninety-one patients treated with PRA, 50 with ROP and 37 with ROT were enrolled in the study. Plasma concentration of DAs significantly correlated with weight-adjusted daily dose in all subgroups, although at a given dose, matched plasma concentrations highly varied among patients. Median PRA plasma concentration-to-daily dose ratio (C/D) [(ng/mL)/(mg/kg/d)] was 68% higher in patients >65 years than ≤65 years (158 vs 94, p < 0.001), while was not affected by age in ROP and ROT subgroups. No sex-mediated differences in C/D ratios were observed in any group. Conclusion: These are the first observations on DAs pharmacokinetics in PD patients’ everyday clinical practice. Of relevance, patients over 65yrs may require about one third of PRA dose compared to under 65yrs to achieve the same plasma concentration. Due to the high intersubject variability in plasma concentrations at the same dosage, we speculate that monitoring of plasma DAs might be helpful in the individualization of treatment in selected patients.

AB - Introduction: Pramipexole (PRA), ropinirole (ROP) and rotigotine (ROT) are non-ergoline dopaminergic agonists (DAs) used to treat Parkinson's disease (PD). Clinical pharmacokinetics of DAs is poorly characterized in PD. The main purpose of our study was to investigate the effect of dose, age and sex on steady-state plasma concentrations of DAs in real life PD patients on chronic DAs therapy. Methods: The study was single center, open and prospective. Blood samples for measurement of DAs plasma concentrations were drawn in the morning, at a median 18-h distance from the last DA dose. Results: Ninety-one patients treated with PRA, 50 with ROP and 37 with ROT were enrolled in the study. Plasma concentration of DAs significantly correlated with weight-adjusted daily dose in all subgroups, although at a given dose, matched plasma concentrations highly varied among patients. Median PRA plasma concentration-to-daily dose ratio (C/D) [(ng/mL)/(mg/kg/d)] was 68% higher in patients >65 years than ≤65 years (158 vs 94, p < 0.001), while was not affected by age in ROP and ROT subgroups. No sex-mediated differences in C/D ratios were observed in any group. Conclusion: These are the first observations on DAs pharmacokinetics in PD patients’ everyday clinical practice. Of relevance, patients over 65yrs may require about one third of PRA dose compared to under 65yrs to achieve the same plasma concentration. Due to the high intersubject variability in plasma concentrations at the same dosage, we speculate that monitoring of plasma DAs might be helpful in the individualization of treatment in selected patients.

KW - Clinical pharmacokinetics

KW - Dopaminergic agonists

KW - Parkinson's disease

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U2 - 10.1016/j.parkreldis.2018.11.007

DO - 10.1016/j.parkreldis.2018.11.007

M3 - Article

VL - 61

SP - 111

EP - 117

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

SN - 1353-8020

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