Bioequivalence study of generic nirmatrelvir in healthy volunteers
Nirmatrelvir is an antiviral drug that, in combination with ritonavir, is an effective agent for the etiotropic therapy of patients with mild to moderate COVID-19.The aim of the study was to evaluate bioequivalence of the generic drug nirmatrelvir Аrpaxel in combination with ritonavir and the origin...
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Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute
2023-05-01
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| Series: | Фармация и фармакология (Пятигорск) |
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| Online Access: | https://www.pharmpharm.ru/jour/article/view/1259 |
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| author | R. A. Oseshnyuk A. G. Nikiforova A. Yu. Boroduleva P. D. Sobolev S. A. Lesnichuk B. B. Garyaev A. A. Abramova V. G. Mozgovaya O. V. Filon A. V. Zinkovskaya A. N. Dolgorukova E. K. Khanonina V. G. Ignatiev M. Yu. Samsonov |
| author_facet | R. A. Oseshnyuk A. G. Nikiforova A. Yu. Boroduleva P. D. Sobolev S. A. Lesnichuk B. B. Garyaev A. A. Abramova V. G. Mozgovaya O. V. Filon A. V. Zinkovskaya A. N. Dolgorukova E. K. Khanonina V. G. Ignatiev M. Yu. Samsonov |
| author_sort | R. A. Oseshnyuk |
| collection | DOAJ |
| description | Nirmatrelvir is an antiviral drug that, in combination with ritonavir, is an effective agent for the etiotropic therapy of patients with mild to moderate COVID-19.The aim of the study was to evaluate bioequivalence of the generic drug nirmatrelvir Аrpaxel in combination with ritonavir and the original drug Paxlovid, which is a combination of nirmatrelvir/ritonavir, in a single dose administration to healthy volunteers.Materials and methods. This research was an open-label, randomized, two-period crossover bioequivalence study. It included 2 periods, in each of which the volunteers received either a test drug (nirmatrelvir at the dose of 300 mg) in combination with ritonavir (100 mg), or a reference drug (a combination of nirmatrelvir 300 mg and ritonavir 100 mg), given as a single dose. A wash-out period between each of the administrations was 7 days. The blood sampling to determine the concentration of nirmatrelvir was carried out in the range from 0 to 36 h in each of the study periods. A nirmatrelvir concentration was determined by a validated HPLC-MS/MS method with a lower quantitation limit of 10 ng/mL. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC(0–16) and Cmax of the test drug and reference drugs with the established equivalence limits of 80.00–125.00%.Results. In the study were included 68 healthy volunteers, 67 participants of which were included in the bioequivalence population. The pharmacokinetic parameters of the drugs were comparable to each other. The 90% confidence interval for the ratio of the geometric mean of the maximum drug concentration in the blood plasma and the area under the pharmacokinetic curve «concentration-time» from zero to the last blood draw within 36 hours of nirmatrelvir was 87.26–100.83 and 93.27–103.74%, which meets the criteria for assessing bioequivalence. The test drugs were well tolerated by the volunteers. The incidence of adverse events was similar for the test and reference drugs. No serious adverse events were recorded during the entire study.Conclusion. As a result of this study, bioequivalence of the test and reference drugs has been established. |
| format | Article |
| id | doaj-art-11bc49e419f5407797e34dd4a47e6eb1 |
| institution | Kabale University |
| issn | 2307-9266 2413-2241 |
| language | Russian |
| publishDate | 2023-05-01 |
| publisher | Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute |
| record_format | Article |
| series | Фармация и фармакология (Пятигорск) |
| spelling | doaj-art-11bc49e419f5407797e34dd4a47e6eb12025-08-20T03:59:57ZrusVolgograd State Medical University, Pyatigorsk Medical and Pharmaceutical InstituteФармация и фармакология (Пятигорск)2307-92662413-22412023-05-01111627110.19163/2307-9266-2023-11-1-62-71471Bioequivalence study of generic nirmatrelvir in healthy volunteersR. A. Oseshnyuk0A. G. Nikiforova1A. Yu. Boroduleva2P. D. Sobolev3S. A. Lesnichuk4B. B. Garyaev5A. A. Abramova6V. G. Mozgovaya7O. V. Filon8A. V. Zinkovskaya9A. N. Dolgorukova10E. K. Khanonina11V. G. Ignatiev12M. Yu. Samsonov13Limited Liability Company “Eco-Safety Scientific Research Center”Limited Liability Company “Exacte Labs”Limited Liability Company “Exacte Labs”Limited Liability Company “Exacte Labs”First Moscow State Medical University (Sechenov University)First Moscow State Medical University (Sechenov University)Peoples’ Friendship University of RussiaJoint-Stock Company “R-Pharm”Joint-Stock Company “R-Pharm”Joint-Stock Company “R-Pharm”Joint-Stock Company “R-Pharm”1. First Moscow State Medical University (Sechenov University). 2. Joint-Stock Company “R-Pharm”Joint-Stock Company “R-Pharm”Joint-Stock Company “R-Pharm”Nirmatrelvir is an antiviral drug that, in combination with ritonavir, is an effective agent for the etiotropic therapy of patients with mild to moderate COVID-19.The aim of the study was to evaluate bioequivalence of the generic drug nirmatrelvir Аrpaxel in combination with ritonavir and the original drug Paxlovid, which is a combination of nirmatrelvir/ritonavir, in a single dose administration to healthy volunteers.Materials and methods. This research was an open-label, randomized, two-period crossover bioequivalence study. It included 2 periods, in each of which the volunteers received either a test drug (nirmatrelvir at the dose of 300 mg) in combination with ritonavir (100 mg), or a reference drug (a combination of nirmatrelvir 300 mg and ritonavir 100 mg), given as a single dose. A wash-out period between each of the administrations was 7 days. The blood sampling to determine the concentration of nirmatrelvir was carried out in the range from 0 to 36 h in each of the study periods. A nirmatrelvir concentration was determined by a validated HPLC-MS/MS method with a lower quantitation limit of 10 ng/mL. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC(0–16) and Cmax of the test drug and reference drugs with the established equivalence limits of 80.00–125.00%.Results. In the study were included 68 healthy volunteers, 67 participants of which were included in the bioequivalence population. The pharmacokinetic parameters of the drugs were comparable to each other. The 90% confidence interval for the ratio of the geometric mean of the maximum drug concentration in the blood plasma and the area under the pharmacokinetic curve «concentration-time» from zero to the last blood draw within 36 hours of nirmatrelvir was 87.26–100.83 and 93.27–103.74%, which meets the criteria for assessing bioequivalence. The test drugs were well tolerated by the volunteers. The incidence of adverse events was similar for the test and reference drugs. No serious adverse events were recorded during the entire study.Conclusion. As a result of this study, bioequivalence of the test and reference drugs has been established.https://www.pharmpharm.ru/jour/article/view/1259covid-19bioequivalencepharmacokineticsnirmatrelvirritonavirgeneric drug |
| spellingShingle | R. A. Oseshnyuk A. G. Nikiforova A. Yu. Boroduleva P. D. Sobolev S. A. Lesnichuk B. B. Garyaev A. A. Abramova V. G. Mozgovaya O. V. Filon A. V. Zinkovskaya A. N. Dolgorukova E. K. Khanonina V. G. Ignatiev M. Yu. Samsonov Bioequivalence study of generic nirmatrelvir in healthy volunteers Фармация и фармакология (Пятигорск) covid-19 bioequivalence pharmacokinetics nirmatrelvir ritonavir generic drug |
| title | Bioequivalence study of generic nirmatrelvir in healthy volunteers |
| title_full | Bioequivalence study of generic nirmatrelvir in healthy volunteers |
| title_fullStr | Bioequivalence study of generic nirmatrelvir in healthy volunteers |
| title_full_unstemmed | Bioequivalence study of generic nirmatrelvir in healthy volunteers |
| title_short | Bioequivalence study of generic nirmatrelvir in healthy volunteers |
| title_sort | bioequivalence study of generic nirmatrelvir in healthy volunteers |
| topic | covid-19 bioequivalence pharmacokinetics nirmatrelvir ritonavir generic drug |
| url | https://www.pharmpharm.ru/jour/article/view/1259 |
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