Comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations Eporon® and Eprex® following a single subcutaneous administration in healthy male volunteers
Sumin Yoon,1 Su-jin Rhee,1 Sun Ju Heo,2 Tae Young Oh,2 Seo Hyun Yoon,1 Joo-Youn Cho,1 SeungHwan Lee,1,3 Kyung-Sang Yu1,3 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Dong-A ST Co. Ltd., Seoul, 3Clinical Trials Center, Seo...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2017-10-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/comparable-pharmacokinetics-and-pharmacodynamics-of-two-epoetin-alfa-f-peer-reviewed-article-DDDT |
| _version_ | 1819128048403873792 |
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| author | Yoon S Rhee SJ Heo SJ Oh TY Yoon SH Cho JY Lee S Yu KS |
| author_facet | Yoon S Rhee SJ Heo SJ Oh TY Yoon SH Cho JY Lee S Yu KS |
| author_sort | Yoon S |
| collection | DOAJ |
| description | Sumin Yoon,1 Su-jin Rhee,1 Sun Ju Heo,2 Tae Young Oh,2 Seo Hyun Yoon,1 Joo-Youn Cho,1 SeungHwan Lee,1,3 Kyung-Sang Yu1,3 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Dong-A ST Co. Ltd., Seoul, 3Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea Purpose: This study aimed to assess and compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties following a single subcutaneous injection of epoetin alfa (Eporon®) with those of the comparator (Eprex®) in healthy male subjects. Subjects and methods: A randomized, double-blind, two-sequence, crossover study was conducted. Subjects were randomly assigned to receive a single dose, that is, 4,000 IU, of the test or comparator epoetin alfa. After 4 weeks, all subjects received the alternative formulation. The primary PK parameters, maximum observed concentration (Cmax) and area under the curve extrapolated to infinity (AUCinf), were calculated with the serum erythropoietin (EPO) concentrations from blood samples collected for 144 h after dosing. The reticulocyte, hematocrit, hemoglobin and red blood cell counts were measured up to 312 h as PD markers. The primary PD parameters, maximum observed effect (Emax) and area under the effect curve (AUEC), were obtained from the baseline-corrected reticulocyte count. The serum EPO concentration and the reticulocyte count were used to assess the concentration–response relationship. The tolerability and immunogenicity profiles were assessed together. Results: Forty-two subjects completed the study. The mean EPO concentration–time profiles were comparable between the two formulations. The geometric mean ratios (90% CI) of the Cmax and AUCinf were 0.908 (0.843–0.978) and 1.049 (0.999–1.101), respectively, both of which were within the regulatory range of 0.80–1.25. Additionally, the PD and tolerability profiles were similar between the two formulations. The time-matched serum EPO concentration and PD markers presented a counterclockwise hysteresis, suggesting a time delay between the measured concentration and the response. Both formulations were well tolerated, and production of anti-drug antibodies was not observed. Conclusion: The two epoetin alfa formulations had similar PK, PD and tolerability profiles. Furthermore, both formulations had a similar time-matched serum EPO concentration and erythropoietic response profile. Thus, the two formulations are expected to be used interchangeably in clinical settings. Keywords: epoetin alfa, erythropoietin, anemia, pharmacokinetics, pharmacodynamics |
| first_indexed | 2024-12-22T08:21:37Z |
| format | Article |
| id | doaj.art-29698ac909d84ea7a3d2746764f8a9ad |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-22T08:21:37Z |
| publishDate | 2017-10-01 |
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| series | Drug Design, Development and Therapy |
| spelling | doaj.art-29698ac909d84ea7a3d2746764f8a9ad2022-12-21T18:32:43ZengDove Medical PressDrug Design, Development and Therapy1177-88812017-10-01Volume 113127313535366Comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations Eporon® and Eprex® following a single subcutaneous administration in healthy male volunteersYoon SRhee SJHeo SJOh TYYoon SHCho JYLee SYu KSSumin Yoon,1 Su-jin Rhee,1 Sun Ju Heo,2 Tae Young Oh,2 Seo Hyun Yoon,1 Joo-Youn Cho,1 SeungHwan Lee,1,3 Kyung-Sang Yu1,3 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Dong-A ST Co. Ltd., Seoul, 3Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea Purpose: This study aimed to assess and compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties following a single subcutaneous injection of epoetin alfa (Eporon®) with those of the comparator (Eprex®) in healthy male subjects. Subjects and methods: A randomized, double-blind, two-sequence, crossover study was conducted. Subjects were randomly assigned to receive a single dose, that is, 4,000 IU, of the test or comparator epoetin alfa. After 4 weeks, all subjects received the alternative formulation. The primary PK parameters, maximum observed concentration (Cmax) and area under the curve extrapolated to infinity (AUCinf), were calculated with the serum erythropoietin (EPO) concentrations from blood samples collected for 144 h after dosing. The reticulocyte, hematocrit, hemoglobin and red blood cell counts were measured up to 312 h as PD markers. The primary PD parameters, maximum observed effect (Emax) and area under the effect curve (AUEC), were obtained from the baseline-corrected reticulocyte count. The serum EPO concentration and the reticulocyte count were used to assess the concentration–response relationship. The tolerability and immunogenicity profiles were assessed together. Results: Forty-two subjects completed the study. The mean EPO concentration–time profiles were comparable between the two formulations. The geometric mean ratios (90% CI) of the Cmax and AUCinf were 0.908 (0.843–0.978) and 1.049 (0.999–1.101), respectively, both of which were within the regulatory range of 0.80–1.25. Additionally, the PD and tolerability profiles were similar between the two formulations. The time-matched serum EPO concentration and PD markers presented a counterclockwise hysteresis, suggesting a time delay between the measured concentration and the response. Both formulations were well tolerated, and production of anti-drug antibodies was not observed. Conclusion: The two epoetin alfa formulations had similar PK, PD and tolerability profiles. Furthermore, both formulations had a similar time-matched serum EPO concentration and erythropoietic response profile. Thus, the two formulations are expected to be used interchangeably in clinical settings. Keywords: epoetin alfa, erythropoietin, anemia, pharmacokinetics, pharmacodynamicshttps://www.dovepress.com/comparable-pharmacokinetics-and-pharmacodynamics-of-two-epoetin-alfa-f-peer-reviewed-article-DDDTepoetin alfaerythropoietinanemiapharmacokineticspharmacodynamics |
| spellingShingle | Yoon S Rhee SJ Heo SJ Oh TY Yoon SH Cho JY Lee S Yu KS Comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations Eporon® and Eprex® following a single subcutaneous administration in healthy male volunteers Drug Design, Development and Therapy epoetin alfa erythropoietin anemia pharmacokinetics pharmacodynamics |
| title | Comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations Eporon® and Eprex® following a single subcutaneous administration in healthy male volunteers |
| title_full | Comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations Eporon® and Eprex® following a single subcutaneous administration in healthy male volunteers |
| title_fullStr | Comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations Eporon® and Eprex® following a single subcutaneous administration in healthy male volunteers |
| title_full_unstemmed | Comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations Eporon® and Eprex® following a single subcutaneous administration in healthy male volunteers |
| title_short | Comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations Eporon® and Eprex® following a single subcutaneous administration in healthy male volunteers |
| title_sort | comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations eporon reg and eprex reg following a single subcutaneous administration in healthy male volunteers |
| topic | epoetin alfa erythropoietin anemia pharmacokinetics pharmacodynamics |
| url | https://www.dovepress.com/comparable-pharmacokinetics-and-pharmacodynamics-of-two-epoetin-alfa-f-peer-reviewed-article-DDDT |
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