Pharmacokinetics of Opicapone and Its Metabolites in Healthy White and Chinese Subjects

Xue, Wei; Tan, Yan; Liu, Yue; Xu, Changjiang; Cong, Duanduan; Zhong, Liping; Song, Jie; Hui, Ai‐Min; Wei, Qi; Wang, Juan; Liu, Xiaohui; Li, Kexin

doi:10.1002/cpdd.922

Cited by 2 publications

(1 citation statement)

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“…Falcão et al found no obvious impact of ethnic factors on pharmacokinetics (PK) and pharmacodynamics (PD) profiles of OPC [ 20 ]. Besides, in a phase 1 study conducted by Xue et al, healthy Chinese and Caucasian subjects showed comparable PK characteristics of OPC after taking 50 mg OPC in multiple doses [ 21 ]. However, very little is known about the exposure–response and safety of OPC when given to the Chinese population.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, Pharmacodynamics, and Tolerability of Opicapone in Healthy Chinese and Caucasian Subjects: An Open-Label, Single-Center, Phase 1 Study

et al. 2022

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Introduction This study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of opicapone (OPC) in healthy Chinese and Caucasian subjects. Methods In this open-label, single-center, phase 1 study, eligible Chinese subjects received one of three OPC doses (25, 50, or 100 mg), and Caucasian subjects received either 25 or 50 mg of OPC. All subjects were administered a single dose of OPC, whereas subjects in the 50-mg OPC group continued to receive once-daily doses of 50 mg OPC for 10 days. The primary endpoint was to evaluate and compare the plasma concentrations and PK parameters of OPC and its main metabolite, and erythrocyte-soluble catechol- O -methyltransferase (S-COMT) activity in Chinese subjects with that of Caucasian subjects. The secondary endpoint was to evaluate the safety of OPC in Chinese subjects. The estimated results for geometric mean ratios (GMRs) were evaluated with the standard bioequivalence (BE) limits between 80% and 125% to evaluate the ethnic differences. All statistical analyses were performed using SAS version 9.4. Results In total, 70 subjects (45 Chinese, 25 Caucasian) were enrolled; the majority of them were male (85.7%). The plasma exposure of both OPC and BIA 9-1103 increased in an approximately dose-proportional manner in both populations. Maximum S-COMT inhibition ranged from 79% to 95% after a single dose and was about 94% after a 10-day once-daily regimen in both populations. The point estimates of GMRs (Chinese/Caucasian) and 90% CI, except C max in 25-mg and 50-mg OPC groups, for PK and PD parameters were within 80% to 125%. Furthermore, no new risks or safety concerns associated with OPC were identified, indicating a tolerable safety profile in healthy Chinese subjects. Conclusion Ethnicity had no significant impact on PK and PD parameters after single or multiple doses of OPC, and OPC was safe and tolerable in healthy Chinese subjects. Trial Registration ChiCTR number, CTR20192230. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-021-00314-8.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, Pharmacodynamics, and Tolerability of Opicapone in Healthy Chinese and Caucasian Subjects: An Open-Label, Single-Center, Phase 1 Study

et al. 2022

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Establishing a Pharmacoinformatics Repository of Approved Medicines: A Database to Support Drug Product Development

Murray,

Bennett-Lenane,

O’Dwyer

et al. 2024

Mol. Pharmaceutics

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Advanced predictive modeling approaches have harnessed data to fuel important innovations at all stages of drug development. However, the need for a machine-readable drug product library which consolidates many aspects of formulation design and performance remains largely unmet. This study presents a scripted, reproducible approach to database curation and explores its potential to streamline oral medicine development. The Product Information files for all centrally authorized drug products containing a small molecule active ingredient were retrieved programmatically from the European Medicines Agency Web site. Text processing isolated relevant information, including the maximum clinical dose, dosage form, route of administration, excipients, and pharmacokinetic performance. Chemical and bioactivity data were integrated through automated linking to external curated databases. The capability of this database to inform oral medicine development was assessed in the context of drug-likeness evaluation, excipient selection, and prediction of oral fraction absorbed. Existing filters of drug-likeness, such as the Rule of Five, were found to poorly capture the chemical space of marketed oral drug products. Association rule learning identified frequent patterns in tablet formulation compositions that can be used to establish excipient combinations that have seen clinical success. Binary prediction models of oral fraction absorbed constructed exclusively from regulatory data achieved acceptable performance (balanced accuracy test = 0.725), demonstrating its modelability and potential for use during early stage molecule prioritization tasks. This study illustrates the impact of highly linked drug product data in accelerating clinical translation and underlines the ongoing need for accuracy and completeness of data reported in the regulatory datasphere.

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Pharmacokinetics of Opicapone and Its Metabolites in Healthy White and Chinese Subjects

Cited by 2 publications

References 25 publications

Pharmacokinetics, Pharmacodynamics, and Tolerability of Opicapone in Healthy Chinese and Caucasian Subjects: An Open-Label, Single-Center, Phase 1 Study

Pharmacokinetics, Pharmacodynamics, and Tolerability of Opicapone in Healthy Chinese and Caucasian Subjects: An Open-Label, Single-Center, Phase 1 Study

Establishing a Pharmacoinformatics Repository of Approved Medicines: A Database to Support Drug Product Development

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