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Pharmacokinetic and pharmacodynamic comparison of ropinirole 24-hour prolonged release and ropinirole immediate release in patients with Parkinson's disease.
Clin Neuropharmacol. 2009 May-Jun; 32(3):140-8.CN

Abstract

OBJECTIVES

To explore the pharmacokinetic-pharmacodynamic relationship between systemic exposure to ropinirole and the primary efficacy end points from two phase 3 studies.

METHODS

Efficacy And Safety Evaluation in Parkinson's Disease (EASE-PD) Monotherapy (101468/168) compared ropinirole 24-hour prolonged release with ropinirole immediate release in patients with early Parkinson's disease (PD). Efficacy And Safety Evaluation in Parkinson's Disease Adjunct (101468/169) compared ropinirole 24-hour prolonged release or placebo in patients with advanced PD not optimally controlled with L-dopa. Sparse blood samples were collected for pharmacokinetic evaluations through population analysis. The relationship between ropinirole systemic exposure [steady-state area under the curve between time zero and 24 hours after dose, AUC(0-24,ss)] and change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) total motor score, and awake time spent off was investigated.

RESULTS

In EASE-PD Monotherapy, the relationship between the decrease in UPDRS motor score and AUC(0-24,ss) was similar for both formulations, with a 60% to 80% probability of response for the exposure range studied. In patients with early PD, similar clinical benefit was achieved at AUC(0-24,ss) values associated with doses of 8 to 12 mg and higher doses (up to 24 mg). In EASE-PD Adjunct, the predicted probability of an off-time response for a patient on placebo was approximately 0.4, increasing to a near total probability of response rate (approximately 0.9) at higher systemic exposures of ropinirole 24-hour prolonged release.

CONCLUSIONS

Characterization of the exposure-response relationship has identified that a dose range of 8 to 12 mg provides clinical benefit for the improvement in UPDRS total motor score in patients with early PD. Similarly, pharmacokinetic-pharmacodynamic analysis showed that, in patients with advanced PD, the probability of response increased with increasing exposures to ropinirole, indicating that doses more than 8 to 12 mg may lead to an improved benefit in parallel with reductions in L-dopa dose.

Authors+Show Affiliations

GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, UK. debra.j.tompson@gsk.comNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18978485

Citation

Tompson, Debra, and Ruth Oliver-Willwong. "Pharmacokinetic and Pharmacodynamic Comparison of Ropinirole 24-hour Prolonged Release and Ropinirole Immediate Release in Patients With Parkinson's Disease." Clinical Neuropharmacology, vol. 32, no. 3, 2009, pp. 140-8.
Tompson D, Oliver-Willwong R. Pharmacokinetic and pharmacodynamic comparison of ropinirole 24-hour prolonged release and ropinirole immediate release in patients with Parkinson's disease. Clin Neuropharmacol. 2009;32(3):140-8.
Tompson, D., & Oliver-Willwong, R. (2009). Pharmacokinetic and pharmacodynamic comparison of ropinirole 24-hour prolonged release and ropinirole immediate release in patients with Parkinson's disease. Clinical Neuropharmacology, 32(3), 140-8. https://doi.org/10.1097/WNF.0B013E318176C505
Tompson D, Oliver-Willwong R. Pharmacokinetic and Pharmacodynamic Comparison of Ropinirole 24-hour Prolonged Release and Ropinirole Immediate Release in Patients With Parkinson's Disease. Clin Neuropharmacol. 2009 May-Jun;32(3):140-8. PubMed PMID: 18978485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic and pharmacodynamic comparison of ropinirole 24-hour prolonged release and ropinirole immediate release in patients with Parkinson's disease. AU - Tompson,Debra, AU - Oliver-Willwong,Ruth, PY - 2008/11/4/pubmed PY - 2009/8/11/medline PY - 2008/11/4/entrez SP - 140 EP - 8 JF - Clinical neuropharmacology JO - Clin Neuropharmacol VL - 32 IS - 3 N2 - OBJECTIVES: To explore the pharmacokinetic-pharmacodynamic relationship between systemic exposure to ropinirole and the primary efficacy end points from two phase 3 studies. METHODS: Efficacy And Safety Evaluation in Parkinson's Disease (EASE-PD) Monotherapy (101468/168) compared ropinirole 24-hour prolonged release with ropinirole immediate release in patients with early Parkinson's disease (PD). Efficacy And Safety Evaluation in Parkinson's Disease Adjunct (101468/169) compared ropinirole 24-hour prolonged release or placebo in patients with advanced PD not optimally controlled with L-dopa. Sparse blood samples were collected for pharmacokinetic evaluations through population analysis. The relationship between ropinirole systemic exposure [steady-state area under the curve between time zero and 24 hours after dose, AUC(0-24,ss)] and change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) total motor score, and awake time spent off was investigated. RESULTS: In EASE-PD Monotherapy, the relationship between the decrease in UPDRS motor score and AUC(0-24,ss) was similar for both formulations, with a 60% to 80% probability of response for the exposure range studied. In patients with early PD, similar clinical benefit was achieved at AUC(0-24,ss) values associated with doses of 8 to 12 mg and higher doses (up to 24 mg). In EASE-PD Adjunct, the predicted probability of an off-time response for a patient on placebo was approximately 0.4, increasing to a near total probability of response rate (approximately 0.9) at higher systemic exposures of ropinirole 24-hour prolonged release. CONCLUSIONS: Characterization of the exposure-response relationship has identified that a dose range of 8 to 12 mg provides clinical benefit for the improvement in UPDRS total motor score in patients with early PD. Similarly, pharmacokinetic-pharmacodynamic analysis showed that, in patients with advanced PD, the probability of response increased with increasing exposures to ropinirole, indicating that doses more than 8 to 12 mg may lead to an improved benefit in parallel with reductions in L-dopa dose. SN - 1537-162X UR - https://www.unboundmedicine.com/medline/citation/18978485/Pharmacokinetic_and_pharmacodynamic_comparison_of_ropinirole_24_hour_prolonged_release_and_ropinirole_immediate_release_in_patients_with_Parkinson's_disease_ L2 - https://doi.org/10.1097/WNF.0B013E318176C505 DB - PRIME DP - Unbound Medicine ER -