Bioequivalence of Two Intravenous Formulations of Antithrombin III: A Two-Way Crossover Study in Healthy Korean Subjects
DC Field | Value | Language |
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dc.contributor.author | Kim, Kyoung-Ah | - |
dc.contributor.author | Urn, Yoon-Young | - |
dc.contributor.author | Kim, Sun-Ho | - |
dc.contributor.author | Park, Ji-Young | - |
dc.date.accessioned | 2021-09-05T19:49:56Z | - |
dc.date.available | 2021-09-05T19:49:56Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2013-11 | - |
dc.identifier.issn | 0149-2918 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/101798 | - |
dc.description.abstract | Background: Treatment with antithrombin (AT)-III is indicated for patients with sepsis or hereditary AT deficiency. Objective: The purpose of this study was to compare the pharmacokinetic and pharmacodynamic characteristics of 2 AT-III formulations in healthy Korean volunteers to satisfy the regulatory requirements for bioequivalence for marketing purposes. Methods: A single-center, single-dose, open-label, randomized, 2-period, 2-sequence crossover study was conducted in healthy Korean volunteers. Blood samples for the drug analysis were collected for up to 216 hours after drug administration. Participants received either the test or reference formulation of AT-III 100 U/kg IV for 20 minutes in the first period and the alternative formulation in the second period. Both the AT-III activity and antigen (Ag) were measured for the analysis of pharmacokinetic properties, and the prothrombin time and the activated partial thromboplastin time were assessed for the analysis of pharmacodynamic properties. Because AT-ill is an endogenous compound, the analysis used data corrected from baseline values. The tolerability of the 2 formulations was also assessed based on physical examinations including vital sign measurements, laboratory tests, and 12-lead ECG. Results: Of the 20 subjects enrolled (mean [SD] age, height, and weight, 25.3 [2.3] years, 175.3 [4.5] cm, and 67.4 [6.3] kg, respectively), 19 completed both treatment periods; 1 subject withdrew consent for personal reasons. The observed mean (SD) C-max, AUC(last), and AUC(0-infinity) of AT-III activity were, respectively, 279.24% (35.92), 14,364.10 (2325.25) % . h, and 17,526.38 (3150.81) % . h with the test formulation and 249.75% (31.96), 12,962.95 (1897.52) % . h, and 15,957.67 (3189.21) % . h with the reference formulation. The observed mean (SD) C-max, AUC(last), and AUC(0-infinity) of AT-III Ag were 62.58 (5.66) mg/dL, 3051.94 (401.87) mg/dL . h, and 3639.80 (726.01) mg/dL h, respectively, with the test formulation and 58.63 (5.27) mg/dL, 2805.08 (272.38) mg/dL h, and 3340.00 (428.46) mg/dL . h with the reference formulation. The geometric mean ratios (90% CI) of the log-transformed data for AT-III activity between the 2 formulations were 1.11494 (1.08994-1.14053) for C-max, 1.11305 (1.05435-1.17503) for AUC(last), and 1.11527 (1.03754-1.19889) for AUC(0-infinity); corresponding values for AT-Ill Ag were 1.08802 (1.06258-1.11405), 1.10905 (1.05804-1.16242), and 1.11460 (1.02058-1.21726). During the study period, 8 adverse events were reported, and all were transient, mild, and resolved completely during the treatment period. Conclusion: The results of the present study showed that these 2 AT-III formulations met the regulatory criteria for pharmacokinetic bioequivalence with respect to AT-III activity and Ag in these healthy Korean subjects. (C) 2013 Elsevier HS Journals, Inc. All rights reserved. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER | - |
dc.subject | DISSEMINATED INTRAVASCULAR COAGULATION | - |
dc.subject | VOLUNTEERS | - |
dc.subject | DEFICIENCY | - |
dc.subject | EPIDEMIOLOGY | - |
dc.subject | THROMBOSIS | - |
dc.subject | HEPARIN | - |
dc.title | Bioequivalence of Two Intravenous Formulations of Antithrombin III: A Two-Way Crossover Study in Healthy Korean Subjects | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Ji-Young | - |
dc.identifier.doi | 10.1016/j.clinthera.2013.08.018 | - |
dc.identifier.scopusid | 2-s2.0-84888000565 | - |
dc.identifier.wosid | 000328098500011 | - |
dc.identifier.bibliographicCitation | CLINICAL THERAPEUTICS, v.35, no.11, pp.1752 - 1761 | - |
dc.relation.isPartOf | CLINICAL THERAPEUTICS | - |
dc.citation.title | CLINICAL THERAPEUTICS | - |
dc.citation.volume | 35 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 1752 | - |
dc.citation.endPage | 1761 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | DISSEMINATED INTRAVASCULAR COAGULATION | - |
dc.subject.keywordPlus | VOLUNTEERS | - |
dc.subject.keywordPlus | DEFICIENCY | - |
dc.subject.keywordPlus | EPIDEMIOLOGY | - |
dc.subject.keywordPlus | THROMBOSIS | - |
dc.subject.keywordPlus | HEPARIN | - |
dc.subject.keywordAuthor | antithrombin III | - |
dc.subject.keywordAuthor | bioequivalence | - |
dc.subject.keywordAuthor | pharmacokinetic equivalence | - |
dc.subject.keywordAuthor | pharmacokinetics | - |
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