An Open-label Randomized Crossover Study with Adaptive Design of the Pharmacokinetics and Bioequivalence of GP30121 and Ceraxon® Corrected for Endogenous Analyte Level
Introduction. Citicoline is an endogenous nucleoside consisting of cytidine and choline linked by a diphosphate bridge that is involved in the synthesis of membrane phospholipids. Drugs containing citicoline have neuroprotective and neurometabolic effects and are used for the treatment of a wide ran...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
LLC Center of Pharmaceutical Analytics (LLC «CPHA»)
2023-09-01
|
| Series: | Разработка и регистрация лекарственных средств |
| Subjects: | |
| Online Access: | https://www.pharmjournal.ru/jour/article/view/1561 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849410716401926144 |
|---|---|
| author | A. N. Arevefa A. R. Dorotenko S. M. Noskov I. E. Makarenko R. V. Drai T. N. Komarov O. A. Archakova N. S. Bagaeva I. E. Shokhin |
| author_facet | A. N. Arevefa A. R. Dorotenko S. M. Noskov I. E. Makarenko R. V. Drai T. N. Komarov O. A. Archakova N. S. Bagaeva I. E. Shokhin |
| author_sort | A. N. Arevefa |
| collection | DOAJ |
| description | Introduction. Citicoline is an endogenous nucleoside consisting of cytidine and choline linked by a diphosphate bridge that is involved in the synthesis of membrane phospholipids. Drugs containing citicoline have neuroprotective and neurometabolic effects and are used for the treatment of a wide range of neurological disorders. In its turn, bioequivalence study is a pathway to register a generic citicoline drug in Russian Federation.Aim. The aim of the study was to investigate the comparative pharmacokinetics (PK) and bioequivalence of two citicoline-containing drugs GP30121 and Ceraxon® in healthy male volunteers when taken on an empty stomach.Materials and methods. We evaluated the pharmacokinetics of citicoline-containing drugs corrected for endogenous analyte (uridine) level using an adaptive design. We determined uridine concentration by high-performance liquid chromatography with mass spectrometric detection. We used R Project software, version 3.6.3. for performing statistical analysis for the study.Results and discussion. GP30121 and Ceraxon® exhibited similar PK profiles. It was shown that the values of 94.12 % confidence interval (CI) at α = 0.0294 for the geometric mean ratios for the primary PK parameters of the main metabolite of the active ingredient of the investigated drugs were fully contained within the predefined equivalence limits of 80.00–125.00 %.Conclusion. The study demonstrates bioequivalence of GP30121 and Ceraxon® proving the approach with the correction for endogenous analyte could be considered in studies of other drugs. |
| format | Article |
| id | doaj-art-ccf7fc38cfed460b835470037a54f63e |
| institution | Kabale University |
| issn | 2305-2066 2658-5049 |
| language | Russian |
| publishDate | 2023-09-01 |
| publisher | LLC Center of Pharmaceutical Analytics (LLC «CPHA») |
| record_format | Article |
| series | Разработка и регистрация лекарственных средств |
| spelling | doaj-art-ccf7fc38cfed460b835470037a54f63e2025-08-20T03:35:00ZrusLLC Center of Pharmaceutical Analytics (LLC «CPHA»)Разработка и регистрация лекарственных средств2305-20662658-50492023-09-0112321822710.33380/2305-2066-2023-12-3-218-2271143An Open-label Randomized Crossover Study with Adaptive Design of the Pharmacokinetics and Bioequivalence of GP30121 and Ceraxon® Corrected for Endogenous Analyte LevelA. N. Arevefa0A. R. Dorotenko1S. M. Noskov2I. E. Makarenko3R. V. Drai4T. N. Komarov5O. A. Archakova6N. S. Bagaeva7I. E. Shokhin8CJSC "Pharm Holding"; Pavlov First Saint Petersburg State Medical University (Pavlov University)CJSC "Pharm Holding"; Pavlov First Saint Petersburg State Medical University (Pavlov University)Clinical Hospital No. 3CJSC "Pharm Holding"; Federal State Budgetary Educational Institution of Higher Education "A. I. Evdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian FederationCJSC "Pharm Holding"LLC "Center for Pharmaceutical Analytics"LLC "Center for Pharmaceutical Analytics"LLC "Center for Pharmaceutical Analytics"LLC "Center for Pharmaceutical Analytics"Introduction. Citicoline is an endogenous nucleoside consisting of cytidine and choline linked by a diphosphate bridge that is involved in the synthesis of membrane phospholipids. Drugs containing citicoline have neuroprotective and neurometabolic effects and are used for the treatment of a wide range of neurological disorders. In its turn, bioequivalence study is a pathway to register a generic citicoline drug in Russian Federation.Aim. The aim of the study was to investigate the comparative pharmacokinetics (PK) and bioequivalence of two citicoline-containing drugs GP30121 and Ceraxon® in healthy male volunteers when taken on an empty stomach.Materials and methods. We evaluated the pharmacokinetics of citicoline-containing drugs corrected for endogenous analyte (uridine) level using an adaptive design. We determined uridine concentration by high-performance liquid chromatography with mass spectrometric detection. We used R Project software, version 3.6.3. for performing statistical analysis for the study.Results and discussion. GP30121 and Ceraxon® exhibited similar PK profiles. It was shown that the values of 94.12 % confidence interval (CI) at α = 0.0294 for the geometric mean ratios for the primary PK parameters of the main metabolite of the active ingredient of the investigated drugs were fully contained within the predefined equivalence limits of 80.00–125.00 %.Conclusion. The study demonstrates bioequivalence of GP30121 and Ceraxon® proving the approach with the correction for endogenous analyte could be considered in studies of other drugs.https://www.pharmjournal.ru/jour/article/view/1561citicolineuridinebioavailabilityadaptive designsafety |
| spellingShingle | A. N. Arevefa A. R. Dorotenko S. M. Noskov I. E. Makarenko R. V. Drai T. N. Komarov O. A. Archakova N. S. Bagaeva I. E. Shokhin An Open-label Randomized Crossover Study with Adaptive Design of the Pharmacokinetics and Bioequivalence of GP30121 and Ceraxon® Corrected for Endogenous Analyte Level Разработка и регистрация лекарственных средств citicoline uridine bioavailability adaptive design safety |
| title | An Open-label Randomized Crossover Study with Adaptive Design of the Pharmacokinetics and Bioequivalence of GP30121 and Ceraxon® Corrected for Endogenous Analyte Level |
| title_full | An Open-label Randomized Crossover Study with Adaptive Design of the Pharmacokinetics and Bioequivalence of GP30121 and Ceraxon® Corrected for Endogenous Analyte Level |
| title_fullStr | An Open-label Randomized Crossover Study with Adaptive Design of the Pharmacokinetics and Bioequivalence of GP30121 and Ceraxon® Corrected for Endogenous Analyte Level |
| title_full_unstemmed | An Open-label Randomized Crossover Study with Adaptive Design of the Pharmacokinetics and Bioequivalence of GP30121 and Ceraxon® Corrected for Endogenous Analyte Level |
| title_short | An Open-label Randomized Crossover Study with Adaptive Design of the Pharmacokinetics and Bioequivalence of GP30121 and Ceraxon® Corrected for Endogenous Analyte Level |
| title_sort | open label randomized crossover study with adaptive design of the pharmacokinetics and bioequivalence of gp30121 and ceraxon r corrected for endogenous analyte level |
| topic | citicoline uridine bioavailability adaptive design safety |
| url | https://www.pharmjournal.ru/jour/article/view/1561 |
| work_keys_str_mv | AT anarevefa anopenlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT ardorotenko anopenlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT smnoskov anopenlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT iemakarenko anopenlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT rvdrai anopenlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT tnkomarov anopenlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT oaarchakova anopenlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT nsbagaeva anopenlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT ieshokhin anopenlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT anarevefa openlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT ardorotenko openlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT smnoskov openlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT iemakarenko openlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT rvdrai openlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT tnkomarov openlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT oaarchakova openlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT nsbagaeva openlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel AT ieshokhin openlabelrandomizedcrossoverstudywithadaptivedesignofthepharmacokineticsandbioequivalenceofgp30121andceraxoncorrectedforendogenousanalytelevel |