Population pharmacokinetics of rotigotine extended-release microspheres for intramuscular injection in patients with early-stage Parkinson's disease
© 2023 British Pharmacological Society..
AIMS: Rotigotine extended-release microspheres is a weekly intramuscular injection formulation to treat Parkinson's disease. This study aimed to develop a population pharmacokinetics (PK) model for rotigotine extended-release microspheres to investigate its PK ethnic differences.
METHODS: Data for the study were obtained from three studies in China, Japan and the US. The population PK model was developed using the Phoenix NLME 8.3.5 software. Two parallel absorption models were created to include both zero- and first-order absorptions. The elimination phase was evaluated for one- and two-compartment linear models. Moreover, covariates including sex, body weight, body mass index, albumin, creatinine clearance and race were input into the model using a stepwise covariate method.
RESULTS: We constructed a one-compartment linear model with the first parallel absorption model identified as the best-fitting model. Simulation results in patients with lighter body weight (45 kg) exhibited a 27% increase in Cmax,ss and a 31% increase in AUCtau,ss compared to those with median body weight (65 kg). Patients with heavier body weight (103 kg) showed a 27% decrease in Cmax,ss and a 29% decrease in AUCtau,ss compared to the median body weight group. Asian patients displayed only a 21% increase in Cmax,ss and a 6% increase in AUCtau,ss compared to non-Asian. While we could not fully conclude that race does not affect rotigotine exposure, dosage adjustments based on race were not deemed necessary.
CONCLUSIONS: Exposure differences were mainly attributed to body weight, while dose adjustments were not needed for patients of different racial identities.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:90 |
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| Enthalten in: |
British journal of clinical pharmacology - 90(2024), 4 vom: 27. März, Seite 1094-1102 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Hong [VerfasserIn] |
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| Links: |
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| Themen: |
87T4T8BO2E |
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| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/bcp.15991 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM366393103 |
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| 245 | 1 | 0 | |a Population pharmacokinetics of rotigotine extended-release microspheres for intramuscular injection in patients with early-stage Parkinson's disease |
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| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 British Pharmacological Society. | ||
| 520 | |a AIMS: Rotigotine extended-release microspheres is a weekly intramuscular injection formulation to treat Parkinson's disease. This study aimed to develop a population pharmacokinetics (PK) model for rotigotine extended-release microspheres to investigate its PK ethnic differences | ||
| 520 | |a METHODS: Data for the study were obtained from three studies in China, Japan and the US. The population PK model was developed using the Phoenix NLME 8.3.5 software. Two parallel absorption models were created to include both zero- and first-order absorptions. The elimination phase was evaluated for one- and two-compartment linear models. Moreover, covariates including sex, body weight, body mass index, albumin, creatinine clearance and race were input into the model using a stepwise covariate method | ||
| 520 | |a RESULTS: We constructed a one-compartment linear model with the first parallel absorption model identified as the best-fitting model. Simulation results in patients with lighter body weight (45 kg) exhibited a 27% increase in Cmax,ss and a 31% increase in AUCtau,ss compared to those with median body weight (65 kg). Patients with heavier body weight (103 kg) showed a 27% decrease in Cmax,ss and a 29% decrease in AUCtau,ss compared to the median body weight group. Asian patients displayed only a 21% increase in Cmax,ss and a 6% increase in AUCtau,ss compared to non-Asian. While we could not fully conclude that race does not affect rotigotine exposure, dosage adjustments based on race were not deemed necessary | ||
| 520 | |a CONCLUSIONS: Exposure differences were mainly attributed to body weight, while dose adjustments were not needed for patients of different racial identities | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a body weight | |
| 650 | 4 | |a population pharmacokinetics model | |
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| 650 | 4 | |a rotigotine extended‐release microspheres | |
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| 700 | 1 | |a Li, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Hongtao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chunli |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Pinglan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Wanhui |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Piu |e verfasserin |4 aut | |
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